〔Abstract〕 Objective To explore the material basis and mechanism of Yindan Xinnaotong soft capsule(YD) in treating myocardial ischemia-reperfusion injury(MIRI) based on network pharmacology, so as to provide theoretical reference for the treatment of MIRI. Methods The main active components and action targets of YD were searched by TCMSP, SwissTargetPrediction and China knowledge Network. The disease targets of MIRI were screened by GeneCards database. The “ drug-component-disease-target” network relationship was constructed by Cytoscape software, enrichment analysis and prediction mechanism were analyzed, and the molecular docking verification was carried out between the top three main active components and the top six targets in PPI network. Human myocardial AC-16 cells were constructed hypoxia/reoxygenation(H/R) model to initially verify the core target. Using CCK-8 assay was usedto detect cell viability and explore the optimal drugconcentration. The influence of YD on cell morphology was observed by using optical microscope. LDH content was detected to assess the integrity of cell membrane; Western blot was used to detect the expression of STAT3, p-STAT3, PI3 K, AKT1 and p-AKT1.Results A total of 105 active components, 382 drug targets, 1223 MIRI disease targets and 160 drug-disease common targets of YD were obtained. The key targets involved AKT1, STAT3, VEGFA,TNF, MAPK8, PIK3 CA and so on. GO analysis mainly involved apoptosis, lipolysis, muscle cell proliferation, cytokine-mediated inflammation,oxidative stress and so on. The results of molecular docking showed that VEGFA, APP and PIK3 CA could bind to quercetin, luteolin and kaempferol. Our results showed that 200 mg/L YD could significantly promote the proliferation of AC-16 cells and reduce LDH leakage. Western blot results showed that YD could activate STAT3 and PI3 KAKT1 signaling pathways and protect myocardium.Conclusion YD can protect MIRI through multi-components,multi-targets and multi-pathways.