In the current study, the possible protective effect of montelukast (Mont, 50 mg/kg, p.o given 2, 24, and 48 h after paraquat injection) against acute paraquat toxicity (PQ, 25 mg/kg i.p.) in rats was evaluated. The effects of treatment on selected oxidative stress parameters in lung tissues as well as certain inflammatory markers in serum were evaluated. The obtained results revealed that Mont can ameliorate the biochemical alterations in the lung tissues which were induced by PQ in rats. This was evidenced by the significant reduction in lung tissues lipid peroxidation, protein carbonyl content and DNA fragmentation, as well as by normalization of glutathione and myeloperoxidase activities. Moreover, the elevated levels of serum TNF-alpha, and LDH induced by paraquat were reversed in Mont-treated rats. Meanwhile, lung paraquat concentration was significantly reduced after Mont treatment compared with PQ alone group. Additionally, a higher survival percentage was observed in rats treated with Mont (80%) compared with the PQ alone group (30%) during 7 days observation. The results indicate that Mont protects lung tissue by balancing oxidant?antioxidant status, inhibiting neutrophil infiltration, and by regulating the generation of inflammatory mediators. In conclusion, the obtained results emphasize the beneficial effect of Mont in ameliorating the toxicity signs of paraquat in rats. The current study greatly recommends the usage of Mont in management of paraquat toxicity.