Diabetic nephropathy (DN) is known to be a leading complication of type 2 diabetes mellitus (T2D). This study evaluated whether the VNTR intron 4 a/b and rs1799983 polymorphisms of endothelial-derived nitric oxide synthase ( eNOS ) gene modulated the risk of developing DN in Asian Indian patients. The eNOS variants were genotyped in 200 patients, 100 with DN and 100 without DN. A significant risk association was observed for the VNTR intron 4 a/b ( p < 0.05). Haplotype analysis revealed that the allele combination of rs1799983894 G/Intron 4b and rs1799983894 T/Intron 4b had a statistically significant inverse association with DN.