Objective: The purpose of this study was to determine pretreatment effects of moderate-term endurance training before the various dosages (10 and 20 mg.kg _1) of DOX on a heat shock protein (HSP70kda) and cardiotoxicity in heart tissue. Methods: Forty-eight male rats were randomly assigned to nontraining (NT) and training (T) groups and three subgroups; DOX10mg.kg -1 and DOX20mg.kg -1 and saline treatment. The training program included treadmill running between 25-39 min/day and 15-17 m/min, 5 days/wk for 3 wk. Result: DOX administration, in particularly with 20mg.kg _1, caused up-regulation of oxidants and cardiac damage (MDA, CK, CPK-MB and CK/ CPK-MB) and down regulation of cardioprotection (HSP70, SOD) markers, as compared to NT+saline group. Pretreatment effect of treadmill running endurance exercise in the presence of DOX with 10 mg.kg _1 caused a significant increase in HSP70, SOD and a significant decrease in MDA and insignificantdecrease in CK, CPK-MB and CK/CPK-MB, in comparison T+DOX10 with NT+DOX10 group. However, there was no significant difference between T+DOX10mg.kg _1 and T+DOX20mg.kg _1 in the aforesaid markers. Conclusion: Dox induced cardiotoxicity is related to oxidative stress. Our study suggests that pretreatment with endurance exercise may be considered as a potentially useful strategy to improve myocardial tolerance against single dose DOX-induced oxidative damage.