To investigate the mechanism of emodin alleviating oxidative damage in diabetic nephropathy mice via cell autophagy mediated by miR-21.Mice were fed with high-sugar and high-fat fodder and streptozotocin was injected intraperitoneally to induce diabetic nephropathy model.Mice of successful model were randomly divided into model group and glimepiride group (0.6 mg/kg/d,ig),emodin high-dose group (50 mg/kg/d,ig),emodin low-dose group (25 mg/kg/d,ig),each group of 10,normal group was also set.After one week of treatment,the blood glucose,kidney weight coefficient and pathological morphology of the mice in each group were measured;renal probe ROS content was measured by fluorescent probe method,and blood urea nitrogen (BUN),creatinine (Cr),and urinary albumin excretion rate were measured by Elisa method;the degree of autophagy of renal cells was observed by transmission electron microscopy,and the expressions of P62,Atg7 and LC3 proteins were determined by Western blot.Compared with the model group,the kidney weight coefficient of the emodin group was significantly reduced (P<0.05),and the renal pathological damage was significantly reduced too;The renal ROS content was significantly reduced (P<0.05),and he content of BUN,Cr,uAE were significantly decreased (P<0.05).What’s more,the degree of autophagy of renal podocytes was significantly enhanced,and miR-21 gene expression was significantly reduced (P<0.05);P62,Atg7,and LC3 protein expressions were significantly increased (P<0.05).Our study indicated that emodin could promote autophagy and reduce oxidative damage in kidneys of DN mice by down-regulating miR-21.