Objective To explore the role and mechanism of cardiac resident macrophages in heart repair after myocardial infarction in mice.Methods Macrophage-specific Cre tool mice(CX3CR1CreER-YFP mice)with doubly transgenic mice(R26tdTomato/DTR mice)were hybridized to obtain cardiac resident macrophage-specific red fluorescent labels in mice.Sixty Cx3crlCreER-YFP:R26Td/DTR hybrid mice were randomly divided into 4 groups:Sham group,DT+Sham group,MI group,and DT+MI group,with 15 mice in each group.MI group and DT+MI group underwent myocardial infarction modeling by ligating the left anterior descending coronary artery.The DT+MI group mice were induced to deplete resident macrophages in the heart tissue using diphtheria toxin(DT)to establish a cardiac resident macrophage knockout model.On the 5th day after myocardial infarction modeling,heart tissue slices of mice were stained with H-E to observe inflammation infiltration and myocardial infarct size were calculated;on the 14th day of modeling,echocardiography was used to measure cardiac function-related parameters in mice,and mRNA expression levels of inflammatory cytokines were detected.Results Compared with the MI group,the DT+MI group mice showed a significant reduction in cardiac resident macrophages([53.75±4.62]vs[6.37±1.25],P＜0.05).On the 14th day after myocardial infarction modeling,compared with the Ml group,the DT+MI group mice had significantly increased left ventricular end-diastolic diameter([5.11±0.22]mm vs[5.92±0.26]mm,P＜0.05)and left ventricular end-systolic diameter([4.77±0.17]mm vs[5.38±0.16]mm,P＜0.05),while the ejection fraction significantly decreased([27.76±1.20]％vs[17.61±0.94]％,P＜0.05);in addition,the DT+MI group mice showed increased expression levels of inflammatory cytokines,increased inflammatory cell infiltration,and significantly larger myocardial infarct size.The protein expression levels of NF-KB/p-P65 in DT+MI group mice were significantly higher than those in the MI group([0.28±0.14]vs[1.09±0.12],P＜0.05).Conclusions Cardiac resident macrophages play an important role in heart tissue repair after myocardial infarction by reducing inflammation cell infiltration and myocardial infarct size.