Objective:To investigate the different model construction methods in diabetic nephropathy(DN) SD rats induced by streptozotocin(STZ) and establish the optimal plan. Methods:Thirty SD rats were randomly divided into 3 groups with 10 rats in each group. A group received intraperitoneal STZ after unilateral nephritic excision;B group received intraperitoneal STZ after unilateral nephritic ligation;C group(control group) received buffer solution only. The changes of body weight(BW),glucose(Glu),serum creatinine (Scr),cholesterol(Chol),triglyceride (TG)and 24-urine protein(24Upro),urine crea(Ucr)were detected every 2 weeks and creatinine clearance rate(Ccr) was calculated. After 11 weeks,the rats were sacrificed,and the kidneys were weighed and taken for pathological examination. Results:There was no significant difference in the model construction periods between the groups A and B. The survival rate of the group B is higher than that of the group A. Conclusion:STZ(55 mg/kg) intraperitoneal injection after unilateral nephritic ligation is the optimal method for inducing rat diabetic nephropathy.