increasing evidence has indicated that mir-155 is closely associated with apoptosis, which may protect the myocardium and diminish the infarct area in myocardial ischemia reperfusion injury (iri). in addition, studies have revealed that mir-155 serves a leading role in promoting fibroblast inflammation, cardiac dysfunction and other aspects of myocardial injury. The present study aimed to uncover the function and potential biological mechanism of miR-155 in myocardial iri. The rat H9c2 myocardial cells was treated with hypoxia/reoxygenation (H/r) to simulate iri in vitro. reverse transcription-quantitative polymerase chain reaction (rT-qPcr) was used to detect the expression levels of mir-155 mrna. cell counting Kit-8 and flow cytometry assays and western blot analysis were applied to determine the biological behaviors of the H/r-treated cells. The association between miR-155 and BAG family molecular chaperone regulator 5 (BAG5) was predicted by bioinformatics software and was confirmed by dual luciferase assay. RT-qPCR and western blot analysis were used to analyze the expression of BAG5. The key proteins involved in mitogen-activated protein kinase (MaPK)/JNK signaling pathway were detected by western blot analysis. The data from the rT-qPcr assay indicated that the expression of mir-155 was markedly upregulated in the H/r model, and that downregulation of mir-155 may promote cell proliferation and inhibit cell apoptosis, and vice versa. BAG5, which was downregulated in the H/R model, was confirmed as a target of miR-155 and negatively modulated by miR-155. The key proteins involved in MaPK/JnK signaling, which were highly expressed in the H/R model, were suppressed by treatment with the miR-155 inhibitor, and overexpression of BAG5 promoted the protective effect of miR-155 inhibition on cell injury caused by H/r. in addition, the expression patterns of hypoxia-inducible factor 1-α and von Hippel-lindau were altered following different treatments. Taken together, the data from the present study indicated that miR-155 inhibition represented a potential treatment strategy to improve myocardial H/R injury, which may be associated with targeting BAG5 and inhibition of the MAPK/JnK pathway.