Objective: Interleukin (IL)-10 is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. IL-10 has met the criteria for an anti-inflammatory and an immunosuppressive cytokine, its activity may be important for clinical outcome of diabetic nephropathy (DN). We aimed at evaluating the relation between the genotypic and allelic frequencies of the IL-10 (-10820/A) polymorphisms, and their association with the risk to develop DN in the Turkish population. Research Design and Methods: The (IL)-10 (-1082G/A) genotypes were retrospectively determined in 43 patients with nephropathy and 48 without nephropathy and a control group of 112 healthy individuals. The polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism. Results: This genotype distribution was different between control subjects and patients with type 2 diabetes in which 24.2% were AA, 75.8% were GA, and 0% were GO (p < 0.001). The frequency of the mutant G allele was 36.1% in patients with diabetes nephropathy versus 39.6% in those without nephropathy (p > 0.05). The genotype frequencies were AA, 27.9%; GA, 72.1%; and GG, 0% in patients with diabetes with nephropathy versus AA, 20.8%; GA, 79.2%; and CC, 0% in those without nephropathy (p > 0.05). Conclusions: The polymorphisms of IL-10 (-10820/A) genes were significantly associated with the occurrence of patients with type 2 diabetes. The IL-10 (-10820/A) genotype and allele frequencies were not different between patients with diabetes with nephropathy and those without nephropathy. Therefore, we conclude that the IL-10 (-10820/A) gene polymorphism is not associated with the development of DN in Turkish patients with type 2 diabetes.