It has been demonstrated that a short-timed ischemia, also called preconditioning (PC), may exert a protective role against a subsequent prolonged stress. This phenomenon is the strongest form of in vivo protection against myocardial ischemic injury. The ischemic PC concept has been extended to PC triggered by non-ischemic stress, such as stretch, some chemicals, hypoxia, and reactive oxygen radicals. The present study was designed to investigate the mechanisms behind hydrogen peroxide preconditioning cardioprotection focusing on antioxidant and phase II enzyme induction and their modulation by mitogen activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K)/Akt.