It is well know that a long period of ischemia followed by reperfusion can create an irreversible tissue damage, also due to the excessive generation of oxygen-derived free radicals. A possibility for avoiding this syndrome is represented by the use of free radical scavengers, such as the superoxide dismutase (SOD). The current authors compared the results achieved through different modifications of this enzyme in an experimental rat hind limb model of ischemia/reperfusion. 60 rats that had a 4 hour and 30 minute ischemia of the left hind limb were divided into four groups of 15 each and treated using a physiological solution (control group), native SOD, monomethoxypolyethylene-glycol-SOD (mPEG-SOD) or poly(acryloilmorpholine)-SOD (PAcM-SOD). The outcomes obtained in terms of limb survival (p < 0.05), as well as histomorphologic studies (p < 0.0005), revealed a superior capacity of mPEG-SOD when compared with the other three substances.