BACKGROUND: Transforming growth factor-beta is known to play a role in the interaction between metabolic and hemodynamic factors in mediating accumulation of extracellular matrix in the diabetic nephropathy. TGF-beta1 gene polymorphism was associated with circulating TGF-beta levels and influenced the pathogenesis of fibrotic diseases including diabetic nephropathy. In this study, we examined the relationship between TGF-beta1 gene codon 10 polymorphism and type 2 diabetic nephropathy with more than 10-year history of disease. METHODS: We conducted a case-control study, which enrolled 325 type 2 diabetes. A total of 176 patients with diabetic nephropathy were compared with 149 patients without diabetic nephropathy. TGF-beta1 codon 10 genotyping was determined using polymerase chain reaction with sequence specific primers method. RESULTS: Distribution of TGF-beta1 codon 10 genotype in the patients either with nephropathy or without nephropathy is confined to Hardy-Weinberg equilibrium. The patients with nephropathy have higher frequency of TGF-beta1 GA/GG genotypes than the patients without nephropathy [GA/GG:AA = 119 (67.6%) : 57 (32.4%) vs. 80 (53.7%) : 69 (46.3%), P < 0.05]. Among patients with diabetic nephropathy, those with TGF-beta1 GA/GG genotypes had higher serum levels of total cholesterol and LDL-cholesterol. CONCLUSION: Our results suggest that TGF-beta1 gene codon 10 polymorphism may contribute to the type 2 diabetic nephropathy.