Objective: In this study, we aimed to test the hypothesis that aerobic exercise might exert its cardio-protective effect by preventing oxidative stress and improving cardiac function in rat models with doxorubicin-induced cardiomyopathy. Design: Randomized controlled trial. Methods: We randomly divided experimental rats into four groups: the normal group was used as a non-cardiomyopathy normal control (n=10); the control group included non-aerobic exercise after doxorubicin-induced cardiomyopathy (n=10); the experimental group I included aerobic exercise (3 m/min) after doxorubicin-induced cardiomyopathy (n=10); and experimental group II included aerobic exercise (8 m/min) after doxorubicin-induced cardiomyopathy. Rats in the treadmill training groups underwent treadmill training, which began at 2 weeks after the first intraperitoneal injection. At the end of the exercise period, we determined the heart weight change for each rat. Changes in the levels of oxidative stress enzymes (superoxide dismutase [SOD], thiobarbituric acid-reactive substances [TBARS], and catalase) in the cardiac tissue of rats from all four groups were examined at the end of the experiment. Results: Significant cardiac myocyte injury and increase in myocardial TBARS concomitant with a reduction in myocardial SOD and catalase were observed following cardiomyopathy (p<0.05). Significant cardiac tissue and increase in myocardial TBARS along with reduction in myocardial SOD and catalase were observed following cardiomyopathy (p<0.05). Oxidative parameters were significantly improved in the aerobic exercise groups compared with the control group. Conclusions: These findings indicate that aerobic exercise effectively prevents oxidative stress in rat models with cardiomyopathy.