We studied the role of cholecystokinin in meal-induced insulin sensitization in rats. Experiments were done with fed or fasted male Wistar rats. Whole-body insulin sensitivity was determined by the rapid insulin sensitivity test in either group. The fed animals were more sensitive to the hypoglycemic effect of insulin than those in the fasted group. Single intravenous doses of proglumide, a cholecystokinin-1 receptor antagonist, decreased insulin sensitivity in fed animals in a dose-dependent manner, whereas it was without effect in the fasted state. We conclude that prandial insulin sensitization strongly depends on pathways regulated by cholecystokinin.