Abstract：Objective：To observe the clinical effect of the therapy of Yishen Huashi Granules combined with Dapagliflozin on diabetic nephropathy (DN) with spleen-kidney qi deficiency syndrome and its effects on the levels of thrombospondin- 1 (TSP- 1) and soluble Axl receptor tyrosine kinase (sAxl). Methods： A total of 88 DN patients with spleen-kidney qi deficiency syndrome were divided into the control group and the observation group according to the random number table method， with 44 cases in each group. The control group was given Dapagliflozin for treatment， and the observation group was treated with Yishen Huashi Granules combined with Dapagliflozin. The traditional Chinese medicine (TCM) syndrome scores， levels of kidney function indexes， blood sugar indexes， and levels of TSP- 1 and sAxl were compared between the two groups；the clinical effects and the incidence of adverse reactions in the two groups were evaluated. Results：After treatment，the total effective rate was 93.18% in the observation group，higher than that of 77.27% in the control group (P＜0.05). After treatment，the TCM syndrome scores，and the levels of urine albumin creatinine ratio (UACR)， urinary albumin excretion rate (UAER)， fasting blood glucose (FBG)，2-hour postprandial glucose (P2hBG) and hemoglobin A1c (HbA1c)，TSP-1 and sAxl in the two groups were lower than those before treatment (P＜0.05)，and the estimated glomerular filtration rate (eGFR) levels were higher than those before treatment (P＜0.05)； the levels of UACR， UAER， TSP- 1， sAxl and blood sugar indexes in the observation group were lower than those in the control group (P＜ 0.05)， and the eGFR level was higher than that in the control group (P＜0.05). There was no significant difference being found in the comparison of incidence of adverse reactions between the two groups (P＞ 0.05). Conclusion： The therapy of Yishen Huashi Granules combined with Dapagliflozin has a significant curative effect on DN with spleen-kidney qi deficiency syndrome，which can effectively improve the kidney function of patients，control the blood sugar and decrease the levels of TSP-1 and sAxl with great safety.