Abstract: The present study was undertaken to evaluate whether stimulation or inhibition of Nitric Oxide (NO) synthesis could affect lung toxicity induced by acute administration of paraquat (PQ) in mice. L-arginine (L-arg.), NG-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG) were employed as NO precursor, competitive and specific NO synthesis inhibitors, respectively. PQ was administered intraperitoneally to Swiss albino mice at a single dose of 50 mg kg-1. L-arg. (700 mg kg-1 day-1), L-NAME (150 mg kg-1 day-1) or AG (100 mg kg-1 day-1) was given in drinking water of mice for 5 days before and one day after PQ administration. Appropriate controls were performed. PQ administration resulted in a pronounced elevation in lipid peroxides (157%) as well as decreased activity of alkaline phosphatase [ALP] (48%) and non-protein thiols (40%) in lung tissue compared to control non-treated mice as evidences of lung injury. Serum level of NO end products, nitrate and nitrite significantly elevated due to PQ administration (150%) as compared to control level. In mice given combined treatment of L-arg. and PQ, a remarkable rise in the serum level of nitrate and nitrite (140%) compared to the PQ group was observed. In addition, L-arg. ameliorated the increased level of lipid peroxides and non-protein thiols depletion as well as the decreased activity of ALP caused by PQ respectively. On the other hand, L-NAME and AG potentiated the deleterious effects of PQ on serum NO, lung lipid peroxides content, non-protein thiols content and alkaline phosphatase activity. In conclusion, PQ-induced lung injury in mice is alleviated by L-arg. but exacerbated by L-NAME and AG supplementation. This could point out to a possible protective role of NO in PQ lung toxicity.