Type 2 diabetes mellitus is one of the most common chronic diseases. This type of diabetes is linked to insulin resistance and compensatory hyperinsulinemia. Human obesity is negatively correlated with insulin sensitivity and is associated with an increased tumor necrosis factor-α (TNF-α) mRNA expression in adipose tissue. TNF-α decreases insulin dependent glucose uptake by inhibiting autophosphorylation of insulin receptor, suggesting that TNF-α may play a role in insulin resistance. In this study, we analysed serum levels of TNF-α of 80 patients with type 2 diabetes mellitus (32 males and 48 females) and 20 healthy control subjects (9 males and 11 females). All cases were subjected to full history, clinical examination and laboratory investigations, including lipid profile, TNF-α, fasting, glucose, and fasting insulin level.According to fasting insulin level insulin resistance index (IRI) was calculated using homeostasis assessment model and according to IRI patients were classified into patients with high IRI and patients with low IRI. We found that TNF-α levels were higher in patients (8.84"6.5 pg/ml) than in control (3.15"0.55 pg/ml), (P=0.000) and TNF-α levels were higher in patients with high IRI (10.95"7.25) than in patients with low IRI (6.53"4.38) (P=0.001). TNF-α levels were elevated both in males and females with no significant sex difference. There was significant correlation between TNF-α and fasting insulin levels. There was insignificant correlation between TNF-α levels and BMI in total diabetic subjects (P>0.05), but the correlation was significant in female patients (P=0.03) which may be explained by their higher degree of obesity. There was no significant correlation between TNF-α and triglycerides and cholesterol levels in diabetic patients but triglycerides and cholesterol levels were statistically higher in patients than in control subjects (P<0.05).We conclude that there is a significant correlation between TNF-α, serum levels and insulin resistance. The higher the IRI is the higher the level of TNF-α which may suggest that TNF-α may be involved in the pathogenesis of type 2 diabetes mellitus.