Anti-diabetic effect of various fractions of Cordyceps militaris (CM), CCCA (crude cordycepin containing adenosine), CMESS (ethanol soluble supernatant), and cordycepin were evaluated in streptozotocin (STZ) induced diabetic mice, CMESS showed potent inhibitory activity of 34.7% in starch-loaded mice (2 g/kg) while acarbose as a positive standard exhibited 37.8% of inhibition rate. After 3 days administration (50 mg/kg), cordycepin (0.2 mg/kg), and acarbose (10 mg/kg) dramatically reduced blood glucose level (inhibition ratio: 46.9%, 48.4% and 37.5% respectively). CCCA that has high contents of cordycepin (0.656 mg/4 mg) did not influence on reducing blood glucose level. The proliferation of splenocytes and peritoneal macrophages derived from STZ-induced diabetic mice administered samples were evaluated out by addition of mitogens to see the stability of the usage of these herbal medicines. Proliferation of T-lymphocyte was significantly decreased; while NO production was increased more than two fold to STZ control in the cordycepin-administered group. Changes of serum enzyme levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were also evaluated. Cordycepin administered group was appeared to acarbose. We conclude that CMESS and cordycepin may be useful tools in the control of blood glucose level in diabetes and promising new drug as an anti-hyperglycemic agent without defects of immune responses and other side effects.