Objective To investigate the long term effects of a high protein diet on glucose metabolism after early postnatal malnutrition in rats with intrauterine growth retardation (IUGR). Methods An IUGR rat model was established by passive smoking. One hundred and twenty nine IUGR pups were assigned randomly into 3 groups: IUGR control group, IUGR low protein group and IUGR high protein group. Forty two normal pups were used as controls. Both the IUGR control group and the non IUGR controls were fed with a 20% (normal) protein diet after birth. Both the low protein and high protein IUGR groups were fed with an 8% low protein diet for the first 4 weeks of life, and then the former were fed with a 20% protein diet, while the latter were fed with a 30% high protein diet. The glucose tolerance test and insulin release test were performed at the 4th, 6th and 48th weeks of life and the insulin sensitive index (ISI) was calculated in the four groups. Results Although the fasting blood glucose was normal in the low protein and high protein groups at the 4th week, the fasting plasma insulin, and blood glucose and insulin concentrations after glucose loading increased and ISI decreased compared with the controls (P< 0.01 ). At the 6th week the fasting blood glucose was normal and the fasting plasma insulin declined, while ISI increased in the low protein and high protein groups. These were significantly different from the controls (P< 0.05 ). By week 48, both the fasting plasma glucose and insulin concentration in the high protein group [( 5.97 ± 0.88 ) mmol/L and ( 42.28 ± 13.36 ) μU/ml, respectively] and the low protein group [( 5.24 ± 1.35 ) mmol/L and ( 31.22 ± 3.36 ) μU/ml, respectively] were significantly higher than those of the controls [( 4.46 ± 1.11 mmol/L and ( 15.82 ± 1.63 μU/ml, respectively]. At the same time, the level of ISI in the high protein group ( 1.32 ± 0.56 ) and the low protein group ( 1.71 ± 0.44 ) declined compared to the controls ( 2.80 ± 0.15 ) (P< 0.01 ). The fasting plasma glucose was normal and the fasting insulin concentration recovered in the IUGR control group. However, after glucose loading, both plasma glucose [( 11.39 ± 1.23 ) mmol/L] and insulin concentrations [( 32.16 ± 4.76 ) μU/ml] were higher than control values [( 7.99 ± 0.92 ) mmol/L and ( 21.70 ± 2.09 ) μU/ml, respectively; P< 0.05 ]. Conclusions A long term high protein diet may result in impaired glucose tolerance and severe insulin resistance in IUGR rats with protein malnutrition in early life. Both intrauterine nutrition and early postnatal nutrition have remarkable long term effects on glucose metabolism in IUGR rats. Objective To investigate the long term effects of a high protein diet on glucose metabolism after early postnatal malnutrition in rats with intrauterine growth retardation (IUGR). Methods An IUGR rat model was established by passive smoking. One hundred and twenty nine IUGR pups were assigned randomly into the three groups: IUGR control group, IUGR low protein group and IUGR high protein group. Forty two normal pups were used as controls. Both the IUGR control group and the non IUGR controls were fed with a 20% (normal) protein diet after birth Both the low protein and high protein IUGR groups were fed with an 8% low protein diet for the first 4 weeks of life, and then the former were fed with a 20% protein diet, while the latter were fed with a 30% high protein diet. The glucose tolerance test and insulin release test were performed at the 4th, 6th and 48th weeks of life and the insulin sensitive index (ISI) was calculated in the four groups. Results Although the fasting blood glucose was normal in the low protein and high protein groups at the 4th week, the fasting plasma insulin, and blood glucose and insulin concentrations after glucose loading increased and ISI decreased compared with the controls (P <0.01). At the 6th week the fasting blood glucose was normal and the fasting plasma insulin declined, while ISI increased in the low protein and high protein groups. These were significantly different from the controls (P <0.05). By week 48, both the fasting plasma glucose and insulin concentration in the high protein group [(5.97 ± 0.88) mmol / L and (42.28 ± 13.36) μU / ml, respectively] and the low protein group [(5.24 ± 1.35) mmol / L and (31.22 ± 3.36) μU / ml, respectively] were significantly higher than those of the controls [(4.46 ± 1.11 mmol / L and (15.82 ± 1.63 μU / ml, respectively]. At the same time, the level of ISI in the high protein group (1.32 ± 0.56 ) and the low protein grou p (1.71 ± 0.44The fasting plasma glucose was normal and the fasting insulin concentration recovered in the IUGR control group. However, after glucose loading, both plasma glucose [(11.39 ± 1.23) mmol / L] and insulin concentrations [(32.16 ± 4.76) μU / ml] were higher than control values ​​[(7.99 ± 0.92) mmol / L and ]. Conclusions A long term high protein diet may result in impaired glucose tolerance and severe insulin resistance in IUGR rats with protein malnutrition in early life. Both intrauterine nutrition and early postnatal nutrition have remarkable long term effects on glucose metabolism in IUGR rats.