Although interferon alpha (IFN alpha) has been widely used for therapy of chronic hepatitis B, no prospective studies have examined the changes in glucose metabolism during IFN alpha therapy in patients with chronic hepatitis B. To study the effects of IFN alpha on glucose metabolism in patients with chronic hepatitis B, we prospectively examined glucose tolerance in 11 patients with chronic hepatitis B before and four weeks after the start of IFN alpha therapy. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were improved after the therapy, compared with before (p < 0.05, respectively). The levels of blood sugar at 30 min and 90 min in a 75 g-oral glucose tolerance test (OGGT), fasting immunoreactive insulin (IRI) and IRI at 90 min in a 75 g-OGTT were decreased (p < 0.05, respectively). Response patterns in 75 g-OGGT before therapy were two patients with a normal pattern, eight with a borderline pattern and one with a diabetic pattern. However, those after therapy were changed to six with a normal pattern, three with a borderline pattern and one with a diabetic pattern. The results of the present study suggest that IFN alpha therapy improves hepatic necro-inflammation in patients with chronic hepatitis B, and that IFN alpha alters glucose metabolism in these patients.