A new side effect of interferon (IFN) therapy, glucose intolerance was investigated using insulin-clamp study. In 75 g oral glucose tolerance tests before and after the IFN therapy showed no significant difference, whereas clamp study showed a significant decrease of glucose disposal. Our data suggested that insulin resistance was the main reason for glucose intolerance observed during INF therapy in the patients with chronic active hepatitis C. Early detection and strict control of glucose intolerance could avoid the progress of glucose intolerance.