We have reported a stable superoxide dismutase (SOD)-like copper complex, Cu-ATSM, which shows high membrane permeability and distribution to the brain or heart. In this study, we evaluated the protective effects of Cu-ATSM on superoxide-mediated tissue damage caused by ischemia-reperfusion using an isolated perfused rat heart model. Lipid peroxidation levels in the Cu-ATSM treated group were lower than those in the non-treated group. Furthermore, released creatine phosphokinase into the perfusate, a marker of tissue damage, was reduced by Cu-ATSM treatment. These results indicated the possibility of Cu-ATSM being an effective SOD-like drug for the treatment of superoxide-mediated damage, such as ischemia-reperfusion injury.