Objective To study the functional and ultramicrostructural effects of melatonin on hypothalamuspituitaryadrenal(HPA) axis in normal and diabetic rats. Methods By means of radioimmunoassay we observed the effects of three doses of melatonin(0.5mg/kg for low, 10mg/kg for medium, 50mg/kg for high) and lipoicin on level of CRH, ACTH and COR in normal and diabetic rats’ plasma for three weeks respectively. The ultramicrostructural changes of hypophysis and pituitary gland after melatonin treatment were also observed under transmission electron microscope(TEM). Results 1 Compared with control groups,the CRH level of melatonin groups in normal and diabetic rats notably reduced (P<0.05). ACTH level of three doses of melatonin and lipoicin treatment groups in normal rats decreased,while mediumdosemelatonin and lipoicin group in diabetic rats markedly fell(P<0.05). COR level turned out the same result with CRH level in normal rats,whereas CRH level in high and medium doses melatonin treated groups of diabetic rats had a significantly reduction trend.2 The melatonin treatment to normal rats had no apparent effect on the ultramicrostructures of hypophysis and pituitary gland cells,but the hypophysis and pituitary gland tissues were targets of diabetic lesion with low metabolism functions. However,our morphological study demonstrated that the melatonin treatment might obviously strengthen the hypophysis and pituitary gland cell metabolism function in resisting the response with diabetic oxidative stress. Conclusion Melatonin can exert inhibiti