Objective  To investigate the effects of tripterygium glycosides on autophagy of renal cells in rats with diabetic nephropathy and to analyze its molecular mechanism.   Methods  A rat model of diabetic nephropathy was made by intraperitoneal injection of streptavidin. Thirty SD rats were randomly divided into 5 groups, control group, model group, 0.1 mg/kg drug group, 0.5 mg/kg drug group and 1.0 mg/kg drug group, and each group has 6 rat. After the successful establishment of the diabetic nephropathy model, the 0.1 mg/kg drug group, the 0.5 mg/kg drug group, and the 1.0 mg/kg drug group were intragastric administration with 0.1, 0.5, and 1.0 mg/kg tripterygium glycosides, respectively, and the control group and the model group were intraperitoneally injected with the same amount of normal saline. The levels of renal function and oxidative stress were compared among groups. The expression levels of p-mammalian target of rapamycin (p-mTOR),mammalian target of rapamycin(mTOR), microtubules associated protein 1 light chain 3β-Ⅱ/microtubules associated protein 1 light chain 3β-Ⅰ(LC3-Ⅱ/LC3-Ⅰ) and Beclin1 protein were detected by Western blotting. The expression levels of  LC3, LC3-Ⅱ and Beclin1 mRNA in each group were detected by Real-time PCR.   Results  Compared with the control group, the serum creatinine(Scr), blood urea nitrogen(BUN), protein(Pro) and malondialdehyde(MDA) levels in the model group increased,and the the glutathione peroxidase(GSH-Px) and catalase(CAT) levels decreased significantly (P<0.05). Compared with the model group, the Scr, BUN, Pro and MDA levels of the drug group were significantly decreased, and GSH-Px and CAT levels were significantly increased in a dose-dependent manner (P<0.05). Compared with the control group, the expression level of p-mTOR protein in the renal tissue of the model group was increased, and the expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin1 protein were decreased (P<0.05). Compared with the model group, the expression level of p-mTOR protein was decreased in the dose group, and the expression levels of LC3-Ⅱ/LC3-Ⅰ protein in the dose group were significantly increased in a dose-dependent manner (P<0.05). The expression levels of Beclin1 protein in the 0.5 mg/kg drug group and 1.0 mg/kg drug group, were  significantly higher than the model group (P<0.05). Compared with the control group, the expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin1 mRNA in the renal tissue of the model group were significantly lower (P<0.05). Compared with the model group, the expression levels of LC3 and Beclin1 mRNA in the drug groups of each dose group were significantly increased (P<0.05).   Conclusion  Tripterygium wilfordii glycosides can protect kidney function in rats with diabetic nephropathy, and its mechanism might be related to inhibition of oxidative stress and activation of autophagy.