The effect of tetrandrine, an active principle of Stephaniae tetrandrae, on the plasma glucose level in streptozotocin-induced diabetic rats (STZ-diabetic rats) was investigated. A single intravenous injection of tetrandrine decreased the plasma glucose in a dose-dependent manner in STZ-diabetic rats. Moreover, tetrandrine (1.0 mg x kg(-1)) significantly attenuated the rise in plasma glucose induced by the intravenous glucose challenge test in normal rats. A stimulatory effect of tetrandrine on glucose uptake was obtained in soleus muscles isolated from STZ-diabetic rats with a concentration-dependent manner from 0.01 to 10.0 micromol L(-1). The increase in glucose utilization by tetrandrine was further characterized using the enhancement of glycogen synthesis in the hepatocytes of STZ-diabetic rats. These results suggest that tetrandrine has the ability to enhance glucose utilization in peripheral tissue, resulting in the lowering of plasma glucose in diabetic rats lacking insulin.