Background: Paraquat (PQ) intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative stress damage. This study aimed to investigate the protective effects and the possible mechanisms of intoxication on rats with acute lung injury (ALI) caused by paraquat poisoning. Methods: Thirty PQ poisoned rats were randomly divided into a PQ intoxication group (intoxication group), a saturated hydrogen saline intervention group (intervention group), and a control group, with 10 rats in each group. The first two groups accepted an intragastric administration of PQ at a dose of 50 mg/kg for every single rat, and the control group was fed with a same volume of normal saline. Five mL/kg of saturated hydrogen saline was given to the intervention group three times a day by peritoneal injection for three days after intoxication. Arterial blood gas was detected on the third day. The rats were executed and their lungs were taken for measurement of wet dry weight ratio, homogenate malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OhdG). Histological changes of the lungs were also observed. Results: Compared with the control group, the intoxication group had more serious hypoxemia, greater wet/dry weight ratio, higher MDA level, higher expression of 8-OhdG and more severe lung damage (P<0.01 or P<0.05). However, after intervention with saturated hydrogen saline, poisoned animals turned to have lighter hypoxemia, smaller wet/dry weight ratio, lower MDA level, lower expression of 8-OhdG, and milder lung damage (P<0.01 or P<0.05). Conclusions: Saturated hydrogen saline is effective in preventing acute lung injury caused by PQ. Possibly, it can neutralize toxic oxygen radicals selectively and alleviate the oxidative stress injury induced by PQ.