Abstract: Objective To investigate the therapeutic effect of sequential therapy with Shou Zhenqi Hua Yuzhuo Formula in patients with stage Ⅲ and Ⅳ diabetic nephropathy. Methods A total of 100 patients with stage Ⅲ and Ⅳ diabetic nephropathy who were treated at Tangshan Hospital of Traditional Chinese Medicine from August 2022 to August 2023 were selected. The control group received conventional western medicine treatment, while the intervention group additionally received the Shou Zhenqi Hua Yuzhuo Formula in stages, with a treatment course of 12 weeks. The traditional Chinese medicine (TCM) syndrome scores, blood glucose, renal function, inflammatory factors, calcium and phosphorus levels were compared between the two groups before treatment, and at 4 and 12 weeks after treatment. Clinical efficacy at 12 weeks post-treatment, and adverse reactions during the treatment period were also compared. Results After 4 and 12 weeks of treatment, the TCM syndrome scores, blood glucose indicators (fasting blood glucose, 2-hour postprandial blood glucose, and fasting insulin) and the levels of inflammation indicators (C-reactive protein, interleukin-6) in the intervention group were significantly lower than those in the control group (P＜0.05). Both groups showed significant reductions in these indicators compared to baseline (P＜0.05). Compared with baseline, both groups exhibited significantly reduced 24-hour urinary protein quantification and serum creatinine levels, along with significantly increased estimated glomerular filtration rate at 4 and 12 weeks after treatment (P＜0.05). Moreover, the above indicators in the intervention group were significantly better than those in the control group at the same time (P＜0.05). Compared with baseline, the blood phosphorus levels and calcium phosphorus product significantly decreased and the blood calcium levels significantly increased in both groups after 4 and 12 weeks of treatment (P＜0.05), and the above indicators in the intervention group were significantly better than those in the control group at the same time (P＜0.05). After 12 weeks of treatment, the total effective rate in the intervention group was significantly higher than that in the control group(P＜0.05).During the treatment period,there was no statistically significant difference in adverse reactions between the two groups (P ＞0.05). Conclusion Sequential therapy of Shou Zhenqi Hua Yuzhuo Formula demonstrates significant efficacy in patients with stage Ⅲ and Ⅳ diabetic nephropathy.It can reduce inflammatory factors,TCM syndrome scores,and blood glucose levels,while improving renal function and calcium and phosphorus metabolism.