Recent data have strongly suggested a role for tumor necrosis factor alpha (TNF-alpha) in the insulin resistance of obesity and diabetes mellitus. The objective of this study was to determine serum TNF- alpha levels in different types of diabetes and diabetic complications, and to evaluate the correlation between serum TNF- alpha and serum insulin, fasting glucose (GLU), triglyceride (TG), and high density lipoprotein cholesterol (HDL-C) and also body mass index (BMI). Serum levels of TNF-alpha in 11 patients with insulin - dependent (Type 1) and 74 patients with non-insulin-dependent (Type 2) diabetes mellitus were examined. In different patterns of diabetes, serum cytokine levels were compared to serum samples obtained from 23 healthy controls. Serum TNF-alpha level was significantly higher in diabetics in comparison to controls (p<0.0001). Cytokine level was found higher in diabetics with nephropathy than retinopathy, but with no significant difference. Also, serum TNF- alpha concentration was higher in diabetics with nephropathy (p<0.05). In patients with retinopathy, serum TNF- alpha concentration was higher than those without any complications but the difference was not significant. We couldn't demonstrate any correlation between serum TNF-alpha and, serum insulin, fasting glucose, TG, HDL-C levels, and BMI. In conclusion, TNF- alpha may be involved in the pathogenesis of diabetes mellitus. However, the measurement of other cytokines (such as IL-1beta, IL-6, and IFN-gamma) together with TNF-alpha may provide additional information in different types of diabetes and diabetic complications.