Background: Nuclear factor kappa-B (NF-觀B) is a transcription factor responsible for rapid responses to cytokines, oxidative stress, and ischemia-reperfusion (I/R) in several tissues. However, it is controversial whether NF-觀B activation during I/R is cardioprotective or not. Methods: We investigated the efficacy of BAY 11-7082, an inhibitor of NF-觀B, in a neonatal cardiomyocyte (CM) and rat myocardial I/R model. I/R was induced by ligation of left anterior descending coronary artery (LAD) for 30 min followed by release. Saline (S) or BAY 11-7082 (130 關g/kg) were given intraperitoneally 15 min after LAD ligation. Results: BAY 11-7082 inhibited phosphorylation of I觀B慣 and nuclear translodation of NF-觀B p65 induced by TNF-慣 (10 ng/mL) in cultured CMs. Induced production of interleukin-8 and vascular cell adhesion molecule-1 from cultured CMs by TNF-慣 was reduced significantly by BAY 11-7082. Infarct size was reduced in BAY 11-7082 treated rats (%MI; 23.1짹5.5 % vs. 10.3짹6.8 %, p=0.031, n=8 in each group) at 24 hours after I/R. BAY 11-7082 preserved fractional shortening (20.4짹5.3 % vs. 31.0짹5.4 %, p=0.001, n=8 in each group) and ejection fraction (46.2짹10.0 % vs. 63.7짹7.9 %, p=0.001, n=8 in each group) at 4 weeks after I/R. The number of apoptotic cardiac myocytes were lower in infarcted myocardium from BAY treated I/R rats (76.5짹21.2 % of control, p=0.042, n=8 in each group). Conclusions: This study suggests that the inhibition of NF-觀B could provide an effective approach to attenuate myocardial I/R injury in acute term and improve ventricular function in chronic term.