In liver diseases, it has been pointed out that pancreatic hypersecretion of insulin is one of the factors which induces hyperreaction of serum insulin after oral glucose loading. Insulin secretion may change according to the stage of liver injury. To address this problem, the glucose tolerance test (GTT) and perifusion of the islets of Langerhans were performed in rats with carbon tetrachloride (CCl(4))-induced liver injury. On the day after administration of CCl(4), ΣIRI increased after GTT, but decreased after perifusion. On the 3rd and 7th days, ΣIRI after GTT and perifusion was normal. These results suggest that in the acute stage of acute liver injury, pancreatic secretion of insulin was reduced and hyperreaction of serum insulin to GTT was probably due to decreased insulin degradation. In the convalescent stage, insulin secretion was normal. During the 3 to 6 weeks of CCl(4) administration, ΣIRI in GTT and perifusion rats did not differ significantly from that of controls. But in the 12th week, ΣIRI after GTT and perifusion increased remarkably. These results suggest that in the early stage of chronic liver injury, pancreatic secretion of insulin does not change, but in the cirrhotic stage, insulin secretion increases, causing hyperreaction of insulin after GTT.