Abstract： Objective： To observe the clinical efficacy of Yishen Tongluo Xiedu Prescription in the adjuvant treatment of diabetic kidney disease（DKD） at stage Ⅲ to Ⅴ and its effect on the NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D（GSDMD）pathway. Methods：A total of 60 patients with DKD at stage Ⅲ to Ⅴ in Jiaxing Hospital of Traditional Chinese Medicine from January 2023 to July 2024 were prospectively selected and divided into the observation group and the control group using the random number table method，with 30 cases in each group. Both groups were given conventional treatment such as hypoglycemic and hypotensive therapy after admission. The control group was treated with Finerenon Tablets on this basis，while the observation group was treated with Yishen Tongluo Xiedu Prescription on the basis of the control group. Both groups were treated for three months continuously. The clinical efficacy and incidence of adverse reactions were compared between the two groups，and the changes in blood glucose indexes [fasting blood glucose（FBG）， glycosylated hemoglobin（HbA1c）， and 2-hour postprandial blood glucose（P2hBG）]， kidney function indexes [serum creatinine（SCr）， 24-hour urinary protein quantification（24 h Upro），and estimated glomerular filtration rate（eGFR）] and the expression levels of NLRP3，Caspase-1 and GSDMD were observed before and after treatment in the two groups. Results：After three months of treatment，the total effective rate was 93.33%（28/30）in the observation group，which was higher than that of 60.00%（18/30）in the control group （P＜0.05）. The levels of FBG， HbA1c， P2hBG， SCr， 24 h Upro， NLRP3， Caspase-1 and GSDMD in the two groups were decreased compared with those before treatment（P＜0.05）. The levels of FBG，HbA1c，P2hBG，SCr， 24 h Upro，NLRP3，Caspase-1 and GSDMD in the observation group were lower than those in the control group（P＜ 0.05）. The level of eGFR in the two groups was increased compared with that before treatment（P＜0.05），and the level of eGFR in the observation group was higher than that in the control group（P＜0.05）. During the treatment， the incidence of adverse reactions in the control group was 6.67%（2/30），while the incidence of adverse reactions in the observation group was 10.00%（3 / 30）， there was no significant difference between the two groups （P＞0.05）. Conclusion： Yishen Tongluo Xiedu Prescription can improve the curative effect of DKD patients at stage Ⅲ to Ⅴ ， improve kidney function and blood glucose levels， and the mechanism may be related to inhibiting the expression of NLRP3/Caspase-1/GSDMD pathway.