Background: Transforming growth factor-beta 1 (TGF-β1) T869C (rs1800470, the same below) gene polymorphism is notably relative with the development of Diabetic Nephropathy (DN) ，and CC/CT genotype diabetic have higher frequency of than TT genotype diabetic. To find out individual risk factors in the two genotypes especially in suscepti-ble genotype could provide more efficient and targeted prevention.Methods: This was a prospective cohort study. A total of 251 type 2 diabetes mellitus (T2DM) patients [53.4% male, 56 (52-67) years] were enrolled in this cohort study. Multiple concerned factors were collected and the relationship of these risk factors and development of DN were evaluated by Cox regression analysis. Hazard ratios of development of DN were calculated by Kaplan-Meier curves and the Cox proportional hazards model for CC/CT genotype versus TT genotype patients.Results: TGF-β T869C gene polymorphism was an independent predictor of DN in T2DM patients (HR, 2.08; 95%CI, 1.18-3.66; P=0.012). Hyperlipemia (HR, 1.91; 95%CI, 1.19-3.08; P=0.007), age (HR, 0.95; 95%CI, 0.93-0.98; P=0.001) and smoking status (HR, 2.36; 95%CI, 1.07-5.21; P=0.033) were risk indictors of the development of DN in CC/CT genotype patients. HbA1c (HR, 2.8; 95%CI, 1.07-7.30; P=0.036), hypertension (HR, 7.46; 95%CI, 1.38-40.29; P=0.02), and hyperlipemia (HR, 12.33; 95%CI, 1.05-145.39; P=0.046) were risk indictors for the development of DN in TT genotype patients.Conclusion: TGF-β T869C gene polymorphism was an independent predictor of DN for T2DM patients and CC/CT genotype had higher susceptibility to DN. CC/CT genotype and TT genotype patients had different risk in-dictors of DN.