OBJECTIVE: To observe therapeutic efficacy and safety of Tripterygium tablets combined with Compound α-keto acid tablets in the treatment of diabetic nephropathy (DN) patients. METHODS: A total of 186 DN patients were randomly divided into control group (93 cases) and study group group (93 cases). Based on routine treatment, control group was given Tripterygium tablet 20 mg orally, 3 times a day; study group was additionally given Compound α-keto acid tablet 3.78 g orally, 3 times a day, on the basis of control group. Both groups were treated for consecutive 3 months. Clinical efficacies of 2 groups were observed, and the levels of renal function indexes (Scr, BUN, CysC, GFR, 24 h urine protein), renal interstitial fibrosis indexes (Hcy, VEGF, HGF, TGF-β1) and oxidative stress indexes (T-AOC, SOD, AOPP, MDA), the occurrence of ADR were also observed before and after treatment. RESULTS: No patient withdrew from the experiment in 2 groups, and all completed the treatment. Total response rate of study group (91.39%) was significantly higher than that of control group (80.65%), with statistical significance (P<0.05). After treatment, the levels of Scr, BUN, CysC and 24 h urine protein, Hcy, VEGF, TGF-β1, AOPP and MDA in 2 groups were significantly lower than before, and the study group was significantly lower than the control group; the levels of GFR, HGF, T-AOC and SOD in 2 groups were significantly higher than before treatment, and the study group was significantly higher than the control group, with statistical significance (P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS: Tripterygium tablets combined with Compound α-keto acid tablets show significant therapeutic efficacy for DN patients but do not increase the occurrence of ADR.