No-reflow phenomenon is a risk factor which severely compromises the benefits of coronary revascularization in patients with acute myocardial infarction. Inflammatory response, as an essential component of cardiac ischemia/reperfusion (I/R) injury, has been suggested to contribute to the myocardial no-reflow. Since nuclear factor kappa B (NF-kappa B) is a key mediator of inflammation, we reasoned that inhibition of NF-kappa B might reduce the extent of no-reflow. To test this hypothesis, the left circumflex coronary arteries of New Zealand white male rabbits were ligated for 1.5 h, followed by reperfusion for 1 h to induce I/R injury. Pretreatment of the rabbits with a specific NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC), significantly attenuated neutrophil infiltration in the no-reflow area as well as the expansion of no-reflow. These beneficial effects were associated with a marked reduction in the serum levels of myocardial induced I/R tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), and CXCL16. Consistently, simulative I/R culture of human umbilical vein endothelial cells (HUVECs) resulted in an increase of TNF-alpha, ICAM-1 and CXCL16, and all of these changes were significantly suppressed by pretreatment of the cells with PDTC or with siRNA-mediated p65 knockdown. Our data thus suggest that inhibition of NF-kappa B may reduce I/R-associated myocardial no-reflow through reduction of myocardial inflammation.