The effect of demethylbellidifolin (DMB), a major compound of Swertia davidi Franch, on ischemia-reperfusion injury was studied in rats. Ischemia-reperfusion injury in vivo and in vitro was induced by 20 min of global ischemia followed 40 min of reperfusion and 60 min of coronary artery occlusion followed 180 min of reperfusion, respectively. DMB (100 or 300 microg/L) significantly improved the recovery of cardiac function during reperfusion in isolated rat hearts, as shown by enhancement of coronary flow, left ventricular pressure and its first derivatives (+/-dp/dt(max)). DMB decreased the release of creatine kinase in coronary effluent as well as the level of malondialdehyde in myocardial tissues. In vivo, DMB (0.5 or 1.0 mg/kg) markedly decreased infarct size and the release of creatine kinase. These results suggest that DMB protects the myocardium against damage due to ischemia-reperfusion in rats. The present study also suggests that the effect of DMB may be related to inhibition of lipid peroxidation.