MicroRNA (miR) has been reported to be associated with ischemia and reperfusion (I/R) and cell apoptosis. Suppression of cell apoptosis may reduce the irreversible damage induced by reperfusion. The aims of the current study were to explore the cytoprotective effects of miR-146 against oxygen-glucose deprivation/recovery (OGD/R)-induced injury in H9c2 rat myocardial cells, as well as the underlying mechanisms. Following stimulation with OGD/R, the cells were transfected with miR-146 mimics or negative controls. The levels of miR-146 were analyzed by reverse transcription-quantitative polymerase chain reaction. Thereafter, cell viability and cell apoptosis were analyzed by MTT assay and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling assay, respectively. In addition, the levels of tumor necrosis factor (TNF)-α were determined by ELISA and the levels of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2 and phosphorylated (p)-nuclear factor (NF)-κB were measured by western blotting. The results demonstrated that overexpression of miR-146 significantly increased cell viability and decreased apoptosis (P<0.05). It was observed that overexpression of miR-146 statistically reduced the levels of Bax, TNF-α and p-NF-κB but markedly upregulated the levels of Bcl-2 (P<0.05). These results indicate that overexpression of miR-146 may protect against OGD/R-induced cardiomyocyte apoptosis. Overexpression of miR-146 may alleviate the irreversible injury associated with reperfusion and the effects may be achieved by inhibiting the NF-κB/TNF-α signaling pathway.