〔Abstract〕 Objective To observe the effect of melatonin(MLT) on diabetic nephropathy(DN) rats, and to explore the mechanism of MLT delaying the progression of DN in rats. Methods Fifteen male SD rats were randomly divided into the normal group, model group and MLT group with 5 rats in each group. Rats in the model group and the MLT group were given 55 mg/kg of streptozotocin(STZ) by intraperitoneal injection in order to establish a DN rat model. After the model was successfully established, rats in the MLT group were given 10 mg/(kg·d)of MLT by intraperitoneal injection, and rats in the normal group and model group were given the equal volume of normal saline. Abdominal aortic blood and kidney tissue of rats were taken 16 weeks after they were given, blood urea nitrogen(BUN) and serum creatinine(SCR) in serum were detected; massion staining was used to observe morphological changes of kidney tissue; β-galactosidase staining(SA-β-gal) was used to detect changes in kidney cell aging; Western blot was used to detect the expression levels of autophagy markers(p62, LC3 B), myosin light chain kinase(MLCK) and cyclin-dependent kinase(CDK) inhibitors(p16, p53, and p21). Results Compared with the normal group, the levels of BUN and SCR in serum in the model group increased, renal interstitial fibrosis was obvious, the autophagy level of kidney tissue decreased, and the expression levels of MLCK, p16, p53, and p21 increased. Compared with the model group, the levels of BUN and SCR in serum in the MLT group decreased, and the aging of the kidney tissue was delayed. After MLT was administered, the pathological damage was significantly reduced, and the autophagy level of kidney tissue was also improved. The expression levels of MLCK, p16, p53 and p21 decreased. Conclusion MLT can improve the progress of DN in DN rats by increasing autophagy and delaying aging.