Abstract: AIM To investigate the protective effects of drag-reducing polymers against ischemia/reperfusion injury in isolated rat heart. METHODS Fifty Wistar rats were randomly divided into five groups: control group, ischemia/reperfusion group (I/R group), low-dose group, middle-dose group and high-dose group. Isolated rat hearts were used to prepare the Langendorff ischemia reperfusion model. Left ventricular peak systolic pressure (LVPSP), left ventricular end diastolic pressure (LVEDP), +dp/dtmax, -dp/dtmax, heart rate and coronary outflow were recorded by multichannel physiological recorder. Levels of lactate dehydrogenase (LDH) in coronary outflow were also detected. RESULTS At the time points of 30 min and 60 min after reperfusion, polyethylene oxide (PEO) was found to have beneficial effects on LVPSP, LVEDP, +dp/dtmax and -dp/dtmax (all P<0.05) in the middle- and high-dose group. Compared with the control group and low-dose group, the middle-dose group and high-dose group were better in maintaining the heart rate (both P<0.05) and increased the coronary outflow (both P<0.05). Levels of LDH in coronary outflow decreased significantly in the middle-dose and high-dose groups (both P<0.05). CONCLUSION As a classic drag-reducing polymer, PEO reduces the fluid resistance of Langendorff ischemia/reperfusion system, improves cardiac systolic and diastolic function, increases coronary outflow and reduces myocardial cell damage and apoptosis, providing a new potential approach for the treatment of myocardial ischemia/reperfusion injury.