Objective: To observe the expression of TLR4 in kidney tissue of rats with diabetic nephropathy and discuss the role of TLR4 in the occurrence and development of the diabetic nephropathy. Methods: A total of 60 clean male SD rats were selected and randomly divided into the modeling group and control group after 1 week of breeding, including 30 rats in each group. Biochemical indices as well as the protein expression of TLR4 were observed and compared between two groups at 2 w, 4 w, 6 w, 8 w and 12 w after the modeling, and the correlation between TLR4 and each biochemical indexes was analyzed. Results: Rats in the modeling group had higher levels of blood glucose, 24-hour urine protein and blood urea nitrogen after the modeling, and showed the increase in the serum creatinine, kidney/body weight ratio, CRP and serum TNF-毩 at 4w after the modeling, with the significant difference compared to results of the control group ( P <0.05). The cross-section area and mean volume of glomerulus in the modeling group at 4 w, 6 w, 8 w and 12 w were significantly higher than those in the control group, with the statistically significant difference ( P <0.05). The expression of TLR4 at each time point in the control group was relatively low. Rats in the modeling group had the high expression of TLR4 in kidney’s glomerular basement membrane, proximal convoluted tubule and renal interstitial area since 2 w, with the significant difference compared to the control group ( P <0.05). The expression in rats of the modeling group was higher than the one of the control group since the 2nd week. As the time flied, its expression increased, with the statistically significant difference between two groups ( P <0.05). There was certain correlation between the protein expression of TLR4 and the increased serum titer of 24hour urine protein excretion, serum creatinine, CRP and TNF-毩. Conclusions: TLR4 may activate the immuno-inflammatory reactions to play a role in the occurrence and development of the diabetic nephropathy. Objective: To observe the expression of TLR4 in kidney tissue of rats with diabetic nephropathy and discuss the role of TLR4 in the occurrence and development of the diabetic nephropathy. Methods: A total of 60 clean male SD rats were selected and distributed divided into the modeling group and control group after 1 week of breeding, including 30 rats in each group. Biochemical indices as well as the protein expression of TLR4 were observed and compared between two groups at 2 w, 4 w, 6 w, 8 w and 12 w after The modeling, and the correlation between TLR4 and each biochemical indexes were analyzed. Results: Rats in the modeling group had higher levels of blood glucose, 24-hour urine protein and blood urea nitrogen after the modeling, and showed the increase in the serum creatinine , kidney / body weight ratio, CRP and serum TNF- 毩 at 4w after the modeling, with significant difference compared to results of the control group (P <0.05). The cross-section area and mean volume of glomerulus in the modeling group at 4 w, 6 w, 8 w and 12 w were significantly higher than those in the control group, with the statistically significant difference (P <0.05). The expression of TLR4 at each time point in the control group was rats in the modeling group had the high expression of TLR4 in kidney’s glomerular basement membrane, proximal convoluted tubule and renal interstitial area since 2 w, with significant difference compared to the control group (P <0.05). The expression in rats of the modeling group was higher than the one of the control group since the 2nd week. As the time flied, its expression increased, with the statistically significant difference between two groups (P <0.05). There was certain correlation between the protein expression of TLR4 and the increased serum titer of 24hour urine protein excretion, serum creatinine, CRP and TNF- 毩. Conclusions: TLR4 may activate the immuno-inflammatory reactions to play a role in the occurrence and developm entof the diabetic nephropathy