Abstract We investigated the mechanism of the hypoglycemic effect of ( R)-4-(1-acetoxyethyl)- N-(cyclohexylcarbamoyl)benzene-sulfonamide [( R)-acetoxyhexamide; ( R)-ACX], a new sulfonylurea compound. ( R)-ACX potently stimulated the release of insulin from cultured pancreatic β-cells (HIT T15 cells), established from hamster islet cells SV40-transformed. When ( R)-ACX was orally administered to fasted rats, it decreased the plasma glucose level in a dose-dependent manner. The hypoglycemic effect of ( R)-ACX was quick and short lasting, as compared to that of acetohexamide and glibenclamide. The quick and short-lasting hypoglycemic effect of ( R)-ACX was thought likely to result from rapid absorption of ( R)-ACX and rapid elimination of ( R)-ACX and its metabolite, ( R)-hydroxyhexamide. Furthermore, ( R)-ACX was found to suppress the increase of blood glucose level due to starch loading in fasted mice. ( R)-ACX may be useful in the control of postprandial hyperglycemia to patients with non-insulin-dependent diabetic mellitus.