The use of methotrexate (MTX), a chemotherapy agent, is limited by a number of side effects, including pulmonary toxicity. Oxidative stress (OS) and inflammation are possible mechanisms of MTX-associated pulmonary toxicity. p-Coumaric acid (PCA) is a phenolic acid that has several beneficial effects on human health, particularly antioxidant and anti-inflammatory. The potential effects of PCA in reducing MTX-induced pulmonary toxicity were investigated in the current study. After MTX (20 mg/kg) was administered to the rats on day 1, two different doses of PCA (2 and 4 mg/kg) were administered intraperitoneally for 3 days and the levels of OS, inflammation and apoptosis were assessed in the lung tissues collected on day 5. PCA applications largely eliminated MTX-induced OS, inflammation and apoptosis in lung tissue via enhancing the capacity of endogenous antioxidant system. The therapeutic effect of PCA against MTX-induced pulmonary toxicity should be re-evaluated in more systematic studies.