Abstract: The present study was carried out to evaluate the anti-diabetic activity of water extract of Calotropis gigantea leaves in alloxan n induced diabetic rats for 0, 20, 60, 120, 240, 360 minutes. The water extract at the dose (0.7 gm/kg) exhibited significant anti-hyperglycemic activity. Oral and intraperitoneally administration of the plant produced significant hypoglycemic effect in normal as well as hyperglycemic rats. The water extract of Calotripis gigantea leaves showed hypoglycemic effect in normoglycemic and hyperglycemic rats after both oral and intraperitoneal administration. The effect could be comparable to that of well-known hypoglycemic compound like metformin and glibenclamide used at 11.3 and 0.13 mg/kg, respectively.