The mechanisms of action of physical agents commonly used to treat skeletal muscle lesions are not well understood. In this study, we examined whether the modulation of oxidative stress is involved in the beneficial effects of cold and heat on gastrocnemius muscle strain injury. Adult male Wistar rats were submitted to a strain injury and treated with therapeutic agents in an isolated or combined form. Strain damage caused an increase in muscle and blood oxidative damage. We suggest that this oxidative damage might be related to the impairment of the muscle cell structure, since we observed a significant positive correlation between increased plasma creatine kinase activity and both oxidized dichlorofluoresceine and lipid peroxidation levels in muscle and blood. The intensity of the inflammatory response appears also to be an important factor in the genesis of oxidative damage immediately following a muscle strain injury. Therapeutic cold seems to be more effective in preventing the damage induced by a strain injury, possibly due to its capacity to control the impairment of muscle cell structure and to modulate the intensity of the inflammatory response that follows a muscle strain injury.