Ischemic heart disease severely endangers health of mankind. Recent advances displayed that myocardial ischemia was relative to a reduction of vagal tone and an increase of sympathetic tone. This article, which is from the view of the change of modulation of cardiac vagal nerve during ischemic heart disease, protective effects of vagal nerve/acetylcholine to ischemic myocardium and the potential way of signal transduction in ischemic preconditioning/postconditioning, summarizes the advances of study on protective effects and mechanisms of vagal nerve and acetylcholine against ischemia injury of myocardium. This review will administer to penetrating understanding to pathogenesis, prevention and cure of ischemic heart disease, and develop the new way for prevention and cure of it.