Aim To investigate the preventive effects of polysaccharide krestin (PSK) on myocardial ischemia reperfusion (I/R) injury. Methods Eight mongrel dogs of male, anesthetized with sodium pentobarbital, underwent 60 min of left anterior descending coronary artery occlusion, followed by 120 min reperfusion (I/R group). Another six dogs (PSK group) were subjected to the same ischemia reperfusion as I/R group, received PSK, which was administered orally, at a dose of 150 mg/kg once daily for two days before thoracotomy. Left ventricular function was evaluated by echocardiography using an echocardiogram and with measurement of left ventricular diastolic pressure (LVDP) by catheterization, and blood samples were taken from coronary venous sinus for the examination of malondialdehyde (MDA), at different time points. The ischemia reperfusion myocardium was examined pathologically. Results LVDP markedly rose before and in early reperfusion in I/R group, but only prior to reperfusion in PSK group. The systolic thickening of ischemia reperfusion myocardium region and left ventricular ejection fraction markedly declined during ischemia in both groups, but progressively improved with the time of reperfusion. In PSK group, the recovery of wall thickening was greater than in I/R group during reperfusion. Plasma MDA concentration during reperfusion in I/R group was higher than its baseline. In PSK group, MDA concentration rose only in early reperfusion, but recovered rapidly. In I/R group, myocardial cellular edema were present and, the fractures of a few myofilaments, the granule loss and swelling of mitochondrias were also seen. The ultrastructural abnormalities were much slighter in PSK group. Conclusion PSK could greatly alleviate the functional impairment and structural abnormalities of ischemia reperfusion myocardium.