The majority of investigations about the cardioprotection induced by opioid preconditioning was focused on the role played by myocardial opioid receptors and the of signal mechanism. However, it has been found that directly activation of the opioid receptors in the central nervous system by intracerebroventricular/intrathecal morphine preconditioning also could mimic cardioprotective effects induced by ischemia preconditioning against ischemia-reperfusion injury, one had found also, the κ-, δ- and μ-ORs of central nervous system were implicated in modulating the protective effect. This effect was probably induced by neurohumoral and analgesic substances.