The antihyperglycemic action of andrographolide, an active principle in the leaves of Andrographis paniculata (Burm. f.) Nees, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats). Oral treatment of andrographolide decreased the plasma glucose concentrations of STZ-diabetic rats in a dose-dependent manner. Similar treatment with andrographolide also decreased the plasma glucose in normal rats and the maximal effect was more marked than that in STZ-diabetic rats. Andrographolide at the effective dose (1.5 mg/kg) significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. In the isolated soleus muscle of STZ-diabetic rats, andrographolide enhanced the uptake of radioactive glucose in a concentration-dependent manner. Moreover, the mRNA and protein levels of the subtype 4 form of the glucose transporter (GLUT4) in soleus muscle were increased after repeated intravenous administration of andrographolide in STZ-diabetic rats for 3 days. These results suggest that andrographolide can increase the glucose utilization to lower plasma glucose in diabetic rats lacking insulin.