The antihyperglycemic effect of catalpol (1) purified from the roots of Rehmannia glutinosa was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats) representing insulin-dependent diabetes mellitus. Bolus intravenous injection of 1 showed antihyperglycemic activity in a dose-dependent manner in STZ-diabetic rats. An effective dose of 0.1 mg/kg 1 significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. Catalpol enhanced the uptake of radioactive glucose in the isolated soleus muscle of STZ-diabetic rats in a concentration-related manner. Moreover, an effect by 1 was established on glycogen incorporation in hepatocytes isolated from STZ-diabetic rats. Catalpol was found to increase glycogen synthesis in STZ-diabetic rats. These results suggest that 1 can increase glucose utilization to lower plasma glucose in diabetic rats lacking insulin.