Objective: To observe the effects and the mechanisms of L-Arginine protects against acute lung injury induced by lipopolysaccharide (LPS). Methods: A total of 45 adult male Wistar rats were randomly divided into three groups as follows: control group (NS group), model group (LPS group) and L-Arginine pretreatment group (L-Arg group). LPS (6 mg/kg) was infused by tail vein to reproduce ALI in LPS group and L-Arg group. L-Arginine (500 mg/kg) was intraperitoneally injected 0.5 h before LPS in L-Arg group, whereas NS group and LPS group were given equivalent volume normal saline. Five rats in each group were killed at 2, 6 and 24 h, meanwhile lung tissue, arterial blood and serum were collected. The PaO2 and W/D were determined at different point of time; serum were collected to determine TNF-α by ELISA, and real time PCR was used to detect the mRNA of iNOS. The content of NO was determined by nitrate reductase method. The pathology changes of lung tissue were observed under light microscope. Results: Rats in the LPS group had sustained hypoxemia, and had a significant increase in W/D, in the concentration of NO and TNF-α, as well as in the pulmonary expression of iNOSmRNA (P<0.05). Under light microscope, interstitial tissue of the lung showed exudation, edema,a great quantity of inflammatory cells accumulation and red blood corpuscle exosmose. Compared with the LPS group, those items in the L-Arg group had a significant improvement (P<0.05), and the pathology of lung tissue was ameliorated at all time than that in LPS group. Conclusion: Pretreatment of L- Arginine could alleviate the inflammatory reaction and protect acute lung injury tissues induced by LPS.