Prandial changes in plasma pancreatic glucagon, blood glucose, and liver glycogen levels were studied during the first meal after 12 h of food deprivation in rats. To determine whether pancreatic glucagon secretion is influenced by the composition of the diet, the experiments were performed in rats fed high-carbohydrate (HC), high-fat (HF), or high-protein (HP) diets. Plasma glucagon levels in the hepatic portal vein increased about 100% during meals in all feeding groups, whereas glucagon levels in the hepatic vein changed very little. Blood glucose concentration in the hepatic portal vein increased during meals in HC diet-fed rats but decreased in HF and in HP diet-fed rats. Blood glucose in the hepatic vein also increased in HC and HP diet-fed rats. In addition, liver glycogen content decreased during meals in HC and HP diet-fed rats and by 14 min after the meal in HF diet-fed rats. These results demonstrate that a considerable amount of the glucagon released during meals in HC, HF, and HP diet-fed rats remains in the liver. This is consistent with the hypothesis that the liver is important for the satiety effect of glucagon. The results also suggest that glucagon contributes to the meal-induced changes in hepatic carbohydrate metabolism observed in all groups.