Abstract：Objective：To observe the clinical effect of Guben Zhuyu Decoction combined with western medicine for early diabetic nephropathy. Methods： A total of 148 cases of patients with early diabetic nephropathy were divided into the control group and the observation group according to the random number table method，with 74 cases in each group. The control group was treated with routine western medicine， and the observation group was additionally treated with Guben Zhuyu Decoction based on the treatment of the control group. Traditional Chinese medicine (TCM) syndrome scores，urine N-acetyl-β-glucosaminidase (NAG)，urinary microalbumin excretion rates (UAER)，and the levels of serum cystatin C (Cys-C)，hypersensitive C-reactive protein (hs-CRP)，interleukin-6 (IL-6)，and tumor necrosis factor-α (TNF-α) were compared before and after treatment between the two groups. Clinical effects and the occurrence of adverse reactions were evaluated in the two groups. Results：The total effective rate was 93.24% in the observation group， higher than that of 78.38% in the control group (P＜0.05). After treatment，TCM syndrome scores，NAG， UAER， and the levels of Cys-C， hs-CRP， IL-6， and TNF- α in the two groups were lower than those before treatment (P＜0.05)，and the above indexes in the observation group were lower than those in the control group (P＜0.05). There was no significant difference being found in the comparison of the incidence of adverse reactions (P＞0.05). Conclusion：Guben Zhuyu Decoction combined with western medicine has a definite curative effect in the treatment of early diabetic nephropathy and can effectively reduce the levels of inflammatory factors and protect kidney function with relatively high safety.