Interferon alpha (IFN alpha) has been widely used as therapy for chronic hepatitis C. However, changes in glucose metabolism during IFN alpha therapy in patients with chronic hepatitis C remain unknown. To study the effects of IFN alpha on glucose tolerance in patients with chronic hepatitis C, we prospectively examined glucose tolerance in 15 patients with chronic hepatitis C before and four weeks after the start of IFN alpha therapy. Serum bilirubin, albumin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) improved after the therapy compared with before (p < 0.05, respectively), while levels of fasting blood sugar, blood sugar at 30 min in 75 g-oral glucose tolerance test (OGGT) and fasting immunoreactive insulin (IRI) decreased (p < 0.05, respectively); insulinogenic index (II) also increased (p < 0.05). Response patterns in 75 g OGGT before therapy were: four patients in normal pattern, five in a borderline pattern and four in a diabetic pattern, whereas those after therapy were changed to four in a normal pattern, and eight in a borderline pattern. Changes in AST between before and after therapy were correlated with those in blood glucose at 30 min in a 75 g-OGGT (r = +0.648, p = 0.042). Although interferons have been reported to impair glucose tolerance in viral infection, the results of the present study indicate that hepatic functional recovery may be associated with improved glucose tolerance in patients with chronic hepatitis C treated with IFN alpha.