Aim:To investigate the effect of the peroxisome proliferator-activator receptor(PPAR)-γ agonist,pioglitazone,on insulin resistance in low-dose streptozotocinand high sucrose-fat diet induced obese rats.Methods:Normal female Wistar ratswere injected intraperitoneally with low-dose streptozotocin(STZ,30 mg/kg)andfed with a high sucrose-fat diet for 8 weeks.Pioglitazone(20 mg/kg)was adminis-tered orally to the obese and insulin-resistant rats for 28 d.Intraperitoneal glu-cose tolerance tests,insulin tolerance tests and gluconeogenesis tests were car-ried out over the last 14 d.At the end of d 28 of the treatment,serums werecollected for biochemical analysis.Glucose transporter 4(GLUT4)and insulinreceptor substrate-1(IRS-1)protein expression in the liver and skeletal musclewere detected using Western blotting.Results:Significant insulin resistance andobesity were observed in low-dose STZ and high sucrose-fat diet induced obeserats.Pioglitazone(20 mg/kg)treatment significantly decreased serum insulin,triglyceride and free fatty acid levels,and elevated high density lipoprotein-cho-lesterol(HDL-C)levels.Pioglitazone also lowered the lipid contents in the liverand muscles of rats undergoing treatment.Gluconeogenesis was inhibited andinsulin sensitivity was improved markedly.The IRS-1 protein contents in the liverand skeletal muscles and the GLUT4 contents in skeletal muscle were elevatedsignificantly.Conclusion:The data suggest that treatment with pioglitazoneimproves insulin sensitivity in low-dose STZ and high sucrose-fat diet inducedobese rats.The insulin sensitizing effect may be associated with amelioratinglipid metabolism,reducing hyperinsulinemia,inhibiting gluconeogenesis,and in-creasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues. Aim: To investigate the effect of the peroxisome proliferator-activator receptor (PPAR) -γ agonist, pioglitazone, on insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats. Methods: Normal female Wistar ratswere injected intraperitoneally with low- Diet streptozotocin (STZ, 30 mg / kg) and fed with a high sucrose-fat diet for 8 weeks. Pioglitazone (20 mg / kg) was adminis- tered orally to the obese and insulin- resistant rats for 28 d. Intraperitoneal glu-cose tolerance tests, insulin tolerance tests and gluconeogenesis tests were car-ried out over the last 14 d. At the end of d 28 of the treatment, serums were collected for biochemical analysis. Glucose transporter 4 (GLUT4) and insulin receptor substrate- 1 (IRS- 1) protein expression in the liver and skeletal musclewere detected using Western blotting. Results: Significant insulin resistance andobesity were observed in low-dose STZ and high sucrose-fat diet induced obeserats.Pioglitazone (20 mg / kg) treatment significantly decreased se rum insulin, triglyceride and free fatty acid levels, and elevated high density lipoprotein-cho-lesterol (HDL-C) levels. Pioglitazone also lowered the lipid contents in the liverand muscles of rats undergoing treatment. Gluconeogenesis was inhibited and insulin sensitivity was improved markedly. The IRS-1 protein contents in the liverand skeletal muscles and the GLUT4 contents in skeletal muscle were elevatedsignificantly. Conlusion: The data suggest that treatment with pioglitazoneimproves insulin sensitivity in low-dose STZ and high sucrose-fat diet inducedobese rats. The insulin sensitizing effect may be associated with amelioratinglipid metabolism, reducing hyperinsulinemia, inhibiting gluconeogenesis, and in-creasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.