The present study was to investigate the hypoglycemic effect of the semi-purified fractions of an ethanolic extract of Mukia maderspatana Linn in streptozotocin-induced diabetic male Wistar albino rats. The hypoglycemic effect of chloroform, butanol and aqueous fractions were assessed by the oral glucose tolerance test at a dose of 100 mg/kg-body weight in streptozotocin -diabetic rats (55 mg/kg i.p.). In the long-term study, the diabetic rats were randomly divided into four groups and treated orally by gavage with vehicle, chloroform fraction (100 mg/kg body weight), butanol fraction (100 mg/kg body weight), and glibenclamide (10 mg/kg body weight) respectively twice a day for 21 days. Hepatic glucose-6-phosphatase activity, glycogen content and thiobarbituric acid reacting substances were also estimated.The data revealed that the chloroform and butanol fractions produced significant blood glucose lowering effect in the diabetic rats and however aqueous fraction did not produce significant change. On day 7, 14 and 21, chloroform and butanol fractions, like the reference drug, glibencalmide, lowered the fasting blood glucose concentration significantly (P < 0.01, P < 0.001) when compared with the diabetic rats. Hepatic glucose-6-phosphatase activity was significantly lower (P < 0.001) in fractions compared to that in diabetic rats. However, there was no change in glycogen content in fractions compared to the diabetic rats. Thiobarbituric acid reacting substances in fractions treated diabetic rats were significantly lower (P < 0.001, P < 0.01) than in diabetic rats.These results indicate that fractions (chloroform and butanol) were potent in the amelioration of hyperglycemia in STZ-diabetic rats and are a potential source for the isolation of new orally active agent(s) for anti-diabetic therapy.