This study examined the effects of ischemia/reperfusion on cardiac function and diabetes-associated lipid peroxidation and scavenger induction in isolated working hearts. Cardiac function in diabetic rats was depressed in proportion to the duration of diabetes. Plasma levels of malondialdehyde (MDA) were increased significantly after diabetes of 1-week duration (1wD). MDA levels in the myocardium were increased significantly after 4-weeks (4wD) and tissue superoxide dismutase (SOD) activity was also elevated significantly in 8-week diabetic rats (8wD) as compared to control values. In both controls and diabetics, tissue MDA concentrations increased significantly during the first 3 min of reperfusion following 20 min of ischemia, compared with preischemia levels. At the end of reperfusion, tissue MDA levels decreased in controls and 1wD hearts, but remained elevated in the 4wD and 8wD cases. The SOD activity in 8wD hearts decreased significantly after 20 min of global ischemia followed by 30 min reperfusion, compared with preischemia levels. By contrast, there were no significant differences between preischemic and after-reperfusion data for parameters of cardiac function in 8wD rats. Thus, lipid peroxidation appears to have little influence on cardiac function during ischemia/reperfusion in rats with chronic diabetes.