Objective: Interleukin-10 (IL-10) polymorphic variants are linked with cytokine production and are involved in many chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). We investigated the hypothesis that IL-10 promoter polymorphisms may be associated with cytokine expressions involved in the progression of diabetic nephropathy (DN). Study Design: A total of 72 Taiwanese subjects were included in this study; along with a control group, patients had a diagnosis of DN lasting ≥2 years, and patients had a diagnosis of T2DM with normal renal functions lasting ≥5 years. Their IL-10 and tumor necrosis factor- α (TNF- α ) genotyping and association of blood chemistry, plasma IL-10, TNF- α , and monocyte chemoattract protein-1 (MCP-1), and urinary MCP-1 were investigated. Results: The IL-10-(-592) genotype exhibited significant association with cytokine expressions in DN: significantly higher TNF- α and lower plasma IL-10 levels were observed in IL-10-(-592)AA, whereas a higher urine MCP-1 level was found in Taiwanese patients with the IL-10-(-592)CC genotype. Conclusions: IL-10-(-592) promoter polymorphisms may influence IL-10 and MCP-1 production, which may be an indicator of nephropathy risk in Taiwanese T2DM patients.