Objective: The aim of this study is to investigate the protective effects of methylprednisolone (MP) and pheniramine maleate (PM) on reperfusion injury of lungs developing after ischemia of the left lower extremity of rats. Materials and methods: A total of 28 randomly selected male rats were divided into 4 groups, each consisting of 7 rats. Group 1 was the control group. Group 2 was the sham group (ischemia/reperfusion [I/R]). Rats in group 3 were subjected to I/R and given PM (Ph group) and rats in group 4 were subjected to I/R and given MP (Pn group). Results: Malondialdehyde levels were significantly lower in Ph group than in I/R group (P < .05). Superoxide dismutase and glutathione peroxidase enzyme activities were found to be significantly higher in Ph group than in the I/R group (P < .05). Histological examination demonstrated that PM had protective effects against I/R injury. Conclusions: The PM has a protective effect against I/R injury in rat lung.