Introduction: In this investigation we aimed to determine whether: (1) physical activity protects rat skeletal muscle from ischemia/reperfusion (I/R) injury; and (2) continued activity after I/R improves the rate of healing. Methods: Rats were divided into sedentary or active (voluntary wheel running) groups. Active rats ran for 4 weeks before I/R or 4 weeks before plus 4 weeks after I/R. Results: Activity before I/R resulted in 73.2% less muscle damage (Evans blue dye inclusion). Sedentary and active rats had a similar decline in neural-evoked (~99%) and directly stimulated (~70%) in vivo muscle torque, and a similar reduction in junctophilin 1. Active rats produced 19% and 15% greater neural-evoked torque compared with sedentary rats at 14 and 28 days postinjury, respectively, although the rate of recovery appeared similar. Conclusions: Activity protects against longterm muscle damage, but not short-term neural injury or excitation- contraction uncoupling. Continued activity neither accelerates nor hinders the rate of functional recovery.