OBJECTIVE： To observe the clinical efficacy and safety of piperazine ferulate combined with glutathione in the treatment of diabetic nephropathy. METHODS： 80 patients with diabetic nephropathy in our hospital were divided into observation group and control group according to random number table， with 40 cases in each group. Both groups was given general treatment as blood glucose， blood lipid and blood pressure control. Control group was additionally given Reduced glutathione tablets 400 mg， tid， on the basis of general treatment. Observation group was additionally given Piperazine ferulate tablets 100 mg， tid， on the basis of control group. Both groups were treated for 12 weeks. The fasting plasma glucose （FPG），2 h postprandial plasma glucose （2 hPG），blood pressure， blood lipid， serum creatinine （Scr），blood urea nitrogen （BUN），24 h urinary total protein and albumin， urine β2 microglobulin （β2-MG） and N-acetyl-β-glucosaminidase （NAG） of 2 groups were detected before and after treatment. The occurrence of ADR was observed. RESULTS： Before treatment， there was no statistical significance in FPG， 2 hPG， blood pressure， blood lipid， Scr， BUN， 24 h urinary total protein and albumin， urine β2-MG and NAG between 2 groups （P＞0.05）. After treatment， above indexes of 2 groups were improved significantly， and the observation group was better than the control group， with statistical significance （P＜0.05）. No obvious ADR was found in 2 groups. CONCLUSIONS： In the treatment of diabetic nephropathy， piperazine ferulate combined with glutathione can improve blood glucose， blood pressure， blood lipid levels and renal function with good safety.