AbstractBackground: Long-term exercise could confer protection against Doxorubicin-induced cardiotoxicity, yet, the effect of short-term exercise just prior to exposure to Doxorubicin (Dox) is still unclear.Aim: To investigate the effect of short-term exercise on cardiac dysfunction induced by Dox treatment.Material and Methods: Sixty nine female albino rats were assigned into 4 groups: Group 1: Control (sedentary rats, n=17), Group 2: Dox (rats received single intraperitoneal injection of Dox in a dose of 20mg/kg, n=18), Group 3: Exc, (n=16), Group 4: Exc +Dox (n=18). Rats were subjected to recording of the ECG, measurement of arterial blood pressure, echocardiograghy, analysis of serum parameters of SGOT, LDH, CPK-MB, troponin I (cTnI) and evaluation of total antioxidant capacity, Malondialdehyde (MDA) and heat shock protein (Hsp20) in the cardiac tissue.Results: Compared to the control, Dox-treated rats showed significant prolongation of QT interval, with insignificant depression of the R voltage and the elevation of systolic (SBP), diastolic (DBP), mean (MAP) blood pressures were statistically insignificant. These changes were accompanied by significant elevation of serum SGOT and cardiac tissue MDA and Hsp20. Also, compared to the control, rats exposed to 3 days exercise just before Dox injection (Exc + Dox) showed significant prolongation of QT even more than in Dox group. However, the depression of the R voltage and the elevation of the SBP, DBP, and MAP become statistically significant compared to the control. These changes were associated with significant increase in SGOT. However, compared to Dox group, the Exc+Dox demonstrated significant prolongation in QT, significant reduction in the ejection fraction with significant reductions in MDA and Hsp20.Conclusion: Short-term swim exercise training just prior to doxorubicin exposure is risky and makes the heart more predisposed to arrhythmia despite of the relative improvement in cardiac oxidative status.