Background and study aim : Hepatitis C is a disease with significant global impact, it is the most common cause of chronic liver diseases, and in addition it causes insulin resistance (IR) leading to increase the risk of type 2 diabetes mellitus (DM). This current study aimed to assess the relationship between serum tumor necrosis factor-α (TNF-α), insulin resistance (IR) and type 2 DM in patients HCV. Patients and Methods: The study cohort consisted of 91 subjects stratified into 4 groups; Group (I): Included 25 HCV patients without DM, Group (II): Included 25 HCV diabetic patients, Group (III): Included 25 diabetic patients without HCV infection and group (IV): Included 16 healthy subjects serving as a control group. All patients were subjected to full history taking, thorough clinical examination and estimation of body mass index (BMI). Anti-HCV Ab was detected by the 3rd generation (ELISA) test and was confirmed by PCR. Assessment of fasting plasma insulin level (FBI) and TNF-α were done by ELISA test, while assessment of the insulin resistance was estimated by Homeostatic Model Assessment (HOMA IR). Results: Higher mean levels of FBS, 2 hr (2HPP) and fasting plasma insulin (FSI) were detected in group II (HCV+DM) compared to other groups with statistically significant differences between all the studied groups (P value