We examined the mode of action of escins Ia (1) and IIa (2) and E,Z-senegin II (3) for the inhibitory effect on the increase in serum glucose levels in oral glucose-loaded rats. Although 1-3 inhibited the increase in serum glucose levels in oral glucose-loaded rats, these compounds did not lower serum glucose levels in normal or intraperitoneal glucose-loaded rats, or alloxan-induced diabetic mice. Furthermore, 1-3 suppressed gastric emptying in rats, and also inhibited glucose uptake in the rat small intestine in vitro. These results indicated that 1-3 given orally have neither insulin-like activity nor insulin-releasing activity. Compounds 1-3 inhibited glucose absorption by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting the glucose transport system at the small intestinal brush border.