Abstract: Myocardial ischemia-reperfusion injury is a great challenge in surgery for myocardial diseases. To mimic myocardial ischemia-reperfusion injury in vitro, H9c2 rat cardiomyoblasts were subjected to oxygen-glucose deprivation/reoxygenation. The purpose of the present study was to explore the effects of tangeretin, a type of flavonoid, on oxygen-glucose deprivation/reoxygenation-induced H9c2 rat cardiomyoblasts. The roles of tangeretin in the viability and lactate dehydrogenase levels of the H9c2 cell were determined using a CCK-8 assay and lactate dehydrogenase detection kit, resp. Then the effects of different doses of tangeretin on the release of inflammatory factors and the level of apoptosis in oxygen-glucose deprivation/reoxygenation-induced cardiomyocytes were evaluated. Following the prediction of the target of tangeretin, Pim-1 proto-oncogene, serine/threonine kinase, through bioinformatics anal., its expression was knocked down. And the influences of Pim-1 proto-oncogene, serine/threonine kinase knockdown on the regulatory roles of tangeretin in oxygen-glucose deprivation/reoxygenation-induced cardiomyocytes were assessed. The results indicated that tangeretin improved the viability of oxygen-glucose deprivation/reoxygenation-induced cardiomyocytes and decreased the lactate dehydrogenase levels. Moreover, tangeretin was found to suppress the release of inflammatory factors and the apoptosis of oxygen-glucose deprivation/reoxygenation-induced cardiomyocytes. Meanwhile, the results revealed that the protective effect of tangeretin on cardiomyocytes undergoing oxygen-glucose deprivation/reoxygenation was broken after Pim-1 proto-oncogene, serine/threonine kinase knockdown. To sum up, the present paper revealed that tangeretin could alleviate the inflammation and the apoptosis of oxygen-glucose deprivation/reoxygenation-induced cardiomyocytes, and protect these cells through activating Pim-1 proto-oncogene, serine/threonine kinase signaling. Graphical abstract: [graphic not available: see fulltext]