The association between Hepatitis C virus (HCV) and diabetes mellitus remains undetermined and must be defined. So, the aim of this work was to study serum insulin, C-peptide and amylase concentrations in patients with chronic hepatitis C virus (CHCV) infection in a trial to search for any pathogenic impact of HCV on both the endocrine and exocrine functions of the pancreatic gland. This work was carried on 75 patients and 20 healthy subjects as controls. All our patients and controls were males and their ages ranged from 40 to 64 years. Patients were classified into diabetic, CHCV, and diabetic with CHCV groups. Each group included 25 males. The results of this work showed a significant increase of S. glucose in diabetics, with and without CHCV (p < 0.001) while liver enzymes (AST & ALT) were significantly increased in CHCV with and without DM (p < 0.001) compared with the control group. Additionally, diabetic group showed a significant increase of S. insulin & C-peptide (p < 0.05) while CHCV group showed a significant Tanta Medical Journal 1290 increase of S. amylase (p < 0.001) compared with the control group. Diabetics with CHCV showed a significant decrease of both serum insulin & C-peptide (p < 0.05) but a significant increase of S. amylase (p < 0.001) compared with the control group. Comparative study of diabetic with CHCV group versus diabetic group and CHCV group, the data showed a significant decrease of S. insulin and C-peptide (P1 < 0.001 & p2 < 0,05), respectively while S. amylase was significantly increased comparing it with DM group, (pi < 0.001) but non-significant change did not occur when compared with CHCV group (P2 > 0.05). We could conclude that; both the exocrine and endocrine parts of the pancreas may be an extrahepatic target of HCV. The disturbances of both insulin & C-peptide associated with CHCV could explain a direct link between HCV and occurrence of diabetes mellitus. So, we recommend to assay S. glucose, insulin & C - peptide levels in every patients with CHCV to predict the incidence of diabetes mellitus.