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Aerial parts of Trichosanthes cucumerina (Family: Cucurbitaceae) are used in traditional medical systems for treatment of diabetes and other diseases. The present study was designed to experimentally evaluate the antidiabetic potential of a hot water extract (HWE) of T. cucumerina (TC) aerial parts. In normoglycemic rats, HWE mediated (a) a dose dependent reduction in fasting blood glucose (FBS) levels (by 35% at 4h post-treatment with dose of 750 mg/kg) and (b) a significant (P<0.05) improvement of glucose tolerance. In STZ-induced diabetic rats, no immediate hypoglycemic effect was observed. However, with continuous administration, there was a gradual reduction in FBS (by 56.8% on day 14 and by 64.4% on day 28). In normoglycemic rats, on day 14 and day 28, the percentage reduction in FBS levels were 41% and 44% respectively. At the end of 28 days, in both normoglycemic and STZ-induced diabetic rats, there was a significant increase in the levels of liver glycogen and adipose tissue triglyceride levels, in comparison with the respective controls that did not receive HWE. However, HWE failed to inhibit intestinal glucose uptake. It may be concluded that T.C can exert significant antidiabetic activity, possibly through multiple effects involving pancreatic and extra pancreatic mechanisms.