Objective:To observe the effect of Yiqi Huoxue Tongluo Recipe on renal fibrosis by regulating the apoptosis of macrophages mediated by Caspase-3/GSDME.Methods:Thirty-six SPF male C57BU6J mice were randomly divided into sham surgery group,unilateral ureteral obstruction(UUO)group,Etanercept group,Yiqi Huoxue Tongluo Recipe group,with 9 mice in each group.Except for the sham surgery group,all other groups of mice were subjected to UUO modeling.After 14 days of treatment,samples were taken for HE,Masson,and Sirius red staining to observe the pathological morphology of kidney tissue.Immunofluorescence double staining for co-expression of F4/80 and GSDME,Western Blot detected α-SMA,Vimentin,Collagen Ⅰ,Caspase-3,GSDME,TNF-α protein expression.Results:Compared with the sham surgery group,the UUO group showed increased renal tubular dilation,atrophy,inflammatory cell infiltration,and collagen deposition;the expression of α-SMA,Vimentin,Collagen Ⅰ,Cleaved Caspase-3,GSDME-N,TNF-α was significantly increased,and the co-expression of F4/80 and GSDME double staining was significantly increased(P<0.05).Compared with the UUO group,the degree of renal tubular injury in each treatment group was significantly improved,collagen deposition was reduced,and the double staining expression of F4/80 and GSDME was significantly reduced,the expression of α-SMA,Vimentin,Collagen Ⅰ,Cleaved Caspase-3,GSDME-N,TNF-α were significantly reduced(P<0.05).Conclusion:Yiqi Huoxue Tongluo Recipe can inhibit TNF-α/Caspase-3/GSDME mediated macrophage apoptosis and improve renal fibrosis.