Spinal cord injury (SCI) results in rapid and significant oxidative stress. We have previously demonstrated that polyethylene glycol (PEG) repairs neuronal membrane and inhibits lipid peroxidation in an in vitro model of SCI. In this study we tested the effects of PEG on oxidative stress in guinea pigs after SCI. Oxidative stress was assessed by lipid peroxidation, protein carbonyl and glutathione content. A compression injury of spinal cord at T10-11 induced a rapid and diffusive oxidative stress. Administration of PEG immediately after injury resulted in a marked decrease in oxidative stress both at the injury site and in its adjacent segments. These results, along with our previous findings, suggest that an early application of PEG can effectively suppress oxidative stress after SCI in vivo.