Using a post-MI ischemic cardiomyopathy model in rat, we demonstrated that the BMC transplantation-mediated benefits, including increased neovascular formation, reduced collagen deposition, increased proliferation activity, favorable modulation of macrophage polarization, and resultant improvement of cardiac function, were all eliminated by antibody-neutralization of HMGB1. Here, HMGB1 is linked to myocardial infarction.