Despite great advances in therapies observed during the last decades, heart failure (HF) remained a major health problem in western countries. In order to further improve symptoms and survival in patients with heart failure, novel therapeutic strategies are needed. In some animal models of HF resveratrol (RES), it was able to prevent cardiac hypertrophy, contractile dysfunction, and remodeling. Several molecular mechanisms are thought to be involved in its protective effects, such as inhibition of prohypertrophic signaling molecules, improvement of myocardial Ca2+ handling, regulation of autophagy, and the reduction of oxidative stress and inflammation. In our present study, we wished to further examine the effects of RES on prosurvival (Akt-1, GSK-3β) and stress signaling (p38-MAPK, ERK 1/2, and MKP-1) pathways, on oxidative stress (iNOS, COX-2 activity, and ROS formation), and ultimately on left ventricular function, hypertrophy and fibrosis in a murine, and isoproterenol- (ISO-) induced postinfarction heart failure model. RES treatment improved left ventricle function, decreased interstitial fibrosis, cardiac hypertrophy, and the level of plasma BNP induced by ISO treatment. ISO also increased the activation of P38-MAPK, ERK1/2Thr183-Tyr185, COX-2, iNOS, and ROS formation and decreased the phosphorylation of Akt-1, GSK-3β, and MKP-1, which were favorably influenced by RES. According to our results, regulation of these pathways may also contribute to the beneficial effects of RES in HF.