Abstract：Objective：To observe the efficacy and safety of Guben Peiyuan Decoction in the treatment of diabetic nephropathy. Methods： A total of 60 patients with diabetic nephropathy treated in Shandong Xinzhonglu Hospital of Traditional Chinese Medicine from June 2021 to December 2022 were selected and randomly divided into a control group and an observation group （30 cases each）. The control group received conventional modern medical treatment， while the observation group received Guben Peiyuan Decoction in addition to the conventional treatment. Clinical efficacy and the incidence of adverse reactions were compared between the two groups. Before and after treatment， the two groups were compared in terms of serum renal fibrosis markers [laminin （LN）， hyaluronic acid （HA）， type Ⅲ procollagen （PCⅢ），and typeⅣcollagen （Ⅳ-C）]，serum creatinine （SCr），blood urea nitrogen （BUN），24-hour urinary protein， endogenous creatinine clearance rate （CCr）， blood glucose levels [fasting blood glucose （FBG）， 2-hour postprandial blood glucose （P2hBG）， and glycated hemoglobin （HbA1c）]， blood pressure levels [systolic blood pressure （SBP） and diastolic blood pressure （DBP）]， as well as levels of high-sensitivity C-reactive protein （hs-CRP），procalcitonin （PCT），CD4+，and CD8+ . Results：The total effective rate of clinical efficacy in the observation group was 73.3% （22/30），higher than that of 40.0% （12/30） in the control group，with the difference being significant （P＜0.05）. After treatment， the levels of LN， HA， PCⅢ， and Ⅳ-C decreased in both groups compared with those before treatment （P＜0.05），and the observation group had lower levels of these four serum renal fibrosis markers than the control group （P＜0.05）. After treatment，SCr，BUN，24-hour urinary protein，and urinary β2-microglobulin levels decreased in both groups compared with those before treatment （P＜0.05）， and CCr levels increased （P＜0.05）； the observation group had lower levels of SCr， BUN， 24-hour urinary protein， and urinary β2-microglobulin than the control group （P＜0.05）， and higher CCr levels （P＜0.05）. After treatment， FBG， P2hBG，HbA1c，SBP，and DBP levels decreased in both groups compared with those before treatment （P＜0.05）， and the observation group had lower levels of these five parameters than the control group （P＜0.05）. After treatment， hs-CRP，PCT，and CD8+ levels decreased in both groups compared with those before treatment （P＜0.05），and CD4+ levels increased （P＜0.05）； the observation group had lower levels of hs-CRP， PCT， and CD8+ than the control group （P＜0.05）， and higher CD4+ levels （P＜0.05）. The incidence of adverse reactions was 13.3% （4/30） in the observation group and 6.7% （2/30） in the control group， with no significant difference between the two groups （P＞ 0.05）. Conclusion：Guben Peiyuan Decoction is effective in treating diabetic nephropathy，regulating blood glucose， controlling blood pressure，enhancing renal function，and reducing inflammatory factor levels，with high safety.