Aim To probe into the effect of proteasome inhibitor MG-132 on myocytic apoptosis in rat with myocardial ischemia-reperfusion injury. Methods The ischemia-reperfusion model was established after 30 min ligation of left anterior descending (LAD) coronary artery. MG-132 (0.75 mg/kg in 2 mL DMSO) was injected 5 min prior to reperfusion. Electron microscopy, histology, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) method, and reverse transcription-polymerase chain reaction was applied to observe myocardial cell apoptosis. Results Functional effects of MG-132 on polymorphonnuclear neutrophillic leukocytes(PMN) accumulation, activation of nuclear factor kappa B (NF-κB) p65 mRNA and protein levels, and apoptosis were characterized in rat myocardial tissue. MG-132 time-dependently inhibited myocardial p65 mRNA expression and reduced myocardial apoptotic index (AI) after reperfusion for 2 h, 6 h and 24 h (p<0.01, respectively). Moreover, MG-132 time-dependently decreased Bax protein levels, while increased Bcl-2 protein levels in ischemic and reperfused myocardium (p<0.05), these effects peaked 24 h after reperfusion. Conclusion MG-132 reduced myocardial reperfusion injury by inhibiting myosytic apoptotic cell death and blocking the activation of NF-κB, down-regulating Bax expression and up-regulating Bcl-2 expression as well as elevating Bcl-2/Bax ratio.