BACKGROUND: Acute ischemia in the hind extremities is a dangerous disease that causes irreversible damage. Revascularization procedures are important to prevent muscle damage, but these treatments may induce additional damage, also known as ischemia-reperfusion injury. The role of free radicals as pivotal mediators of ischemia-reperfusion injury remains a prominent hypothesis. We have recently revealed potent antioxidative activities of a novel free-radical scavenger named resorcimoline (RML). The present study aims to investigate RML as a new therapeutic agent to reduce muscle damage and prevent motor dysfunction of the hind extremities caused by acute limb ischemia. METHODS: Ischemia was induced in rats by occluding the femoral arteries in both hind limbs for 120 min with nylon bands, followed by reperfusion for 24 h. The RML group (n = 9) received an intravenous injection of RML immediately before reperfusion, whereas the saline group (n = 9) received an equivalent volume of saline. Motor function was evaluated by counting the number of steps required to return to normal gait. Serum biomarkers, including creatine kinase (CK) and lactate dehydrogenase (LDH), were measured to evaluate muscle injury. Muscle damage was assessed histologically with hematoxylin and eosin (HE) staining. Oxidative damage to DNA in muscle was evaluated by measuring the proportions of 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells by immunohistochemistry. RESULTS: The average number of steps required to return to normal gait in the RML group was significantly smaller compared to the saline group (P = 0.04). Serum CK and LDH levels were significantly lower in the RML group than in the saline group (P = 0.03, P = 0.005). Histologically, the RML group demonstrated a significantly lower proportion of muscle damage (P = 0.004) and positivity of 8-OHdG (P = 0.01). CONCLUSION: RML attenuated muscle damage and demonstrated protective effects against motor dysfunction after limb ischemia-reperfusion injury by reducing free-radical-induced DNA damage. RML can be a novel therapeutic agent that attenuates ischemia-reperfusion injury after acute limb ischemia.