Blockade of angiotensin II type 1 receptor (AT1) signaling attenuates heart failure following myocardial infarction (MI), perhaps through reduction of fibrosis in the noninfarcted myocardium. However, its specific effect on the infarct tissue itself has not been fully clarified, which we examined in the present study. After inducing MI in mice, treatment with the AT1 blocker (ARB) olmesartan, beginning on the 3rd day post-MI, significantly improved survival (94%) 4 weeks post-MI, as compared to saline (53%) and hydralazine (73%). Olmesartan-treated mice also showed significant attenuation of left ventricular dilatation and dysfunction, as well as significantly greater infarct wall thickness, though the absolute size of the infarct scar was unchanged. In addition, significantly greater numbers of nonmyocytes (mainly vascular cells and myofibroblasts) were present within the infarct scar in olmesartan-treated hearts. Ten days post-MI, apoptosis among granulation tissue cells was significantly suppressed in the olmesartan-treated hearts, where expression of Fas, Bax, procaspase-3 and Daxx and activation of caspase-3, c-Jun N-terminal kinase and c-Jun were all significantly attenuated. By contrast, expression of Fas ligand, Bcl-2 and FADD and activation of caspase-8 were unaffected, suggesting olmesartan exerts a negative regulatory effect on the alternate pathway downstream of Fas receptor. In vitro, olmesartan dose-dependently inhibited Fas-mediated apoptosis in granulation tissue-derived myofibroblasts. The present study proposes this antiapoptotic effect as another important mechanism for an ARB in improving post-MI ventricular remodeling as well as its antifibrotic effect and also suggests a significant link between renin-angiotensin and Fas/Fas ligand systems in postinfarction hearts.