Objective：To study the effect of melatonin (Mel),a potent antioxidant,on the oxidative stress and the activity of hypothalamopituitaryadrenal axis in diabetic rats. Methods: Male SD rats were assigned to the following 4 groups:normal control (treated with 2% ethyl alcohol lavage\[NC,n=6\]),diabetes mellitus control (treated with 2% ethyl alcohol lavage \[DM,n=7\]),diabetes mellitus model group 1 (treated with Mel lavage \[10 mg·kg-1·d-1,DM+Mel1,n=6\]), diabetes mellitus model group 2 (treated with Mel lavage \[0.2 mg·kg-1·d-1,DM+Mel2,n=6\]).Diabetes in DM group, DM+Mel1 group and DM+Mel2 group was induced by intraperitoneal injection of streptozotacin(65 mg/kg).Blood glucose,body weight and adrenal gland weight/body weight(AW/BW) were determined in the 4 groups 12 weeks later;malondialdehyde(MDA) was examined with visible spectrophotometry; blood total cholesterol (TC)and triglyceride(TG) were examined with enzymology method; blood corticotrophinreleasing hormone(CRH),adrenocorticotrophic hormone(ACTH) and corticosterone(CORT) were examined with radioimmune method. Results: Blood glucose, MDA , TC, TG,CRH,ACTH,CORT and AW/BW in DM group were significantly higher than those in NC group(P<0.01); and the body weight of rats in DM group were significantly lower those of NC group(P<0.01). Compared with DM group, DM+Mel1 and DM+Mel2 group had a significantly lower blood glucose, MDA ,TC,TG and AW/BW (P<0.01 or P<0.05) and higher body weight (P<0.01). Blood CRH,ACTH and CORT were markedly decreased in DM+Mel1 group(P<0.01); blood CORT were markedly decreased in DM+Mel2 group (P<0.05); blood CRH and ACTH in DM+Mel2 group had no significant changes. Conclusion: Mel may lower the oxidase activity, improve metabolic disorder of glucose and fat, and inhibit the activity of hypothalamopituitaryadrenal axis in diabetic rats, exerting protective effect on diabetic rats.