Objective To study the regulatory effect of Gegen Qinlian decoction ((GQL)) on MAPK/NF-κ B signal pathway and lung tissue protection in rats with acute lung injury induced by lipopolysaccharide (LPS). Methods 75 rats were randomly divided into control group, model group, low, middle and high dose groups of GQL, 15 rats in each group. Except for the control group, the rat model of acute lung injury was established by intraperitoneal injection of lipopolysaccharide ((LPS)). The rats in the low, middle and high dose groups of GQL were given different doses of Gegen Qinlian decoction by intragastric administration according to the dose of 2.5mL/kg, once a day for 8 weeks. The levels of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1 β(IL-1 β) in serum, (PMN) count of neutrophils in bronchoalveolar lavage fluid (BALF), wet / dry weight ratio of lung tissue, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in lung tissue were measured. The lung histopathology of rats was examined by hematoxylin-eosin staining. Real time quantitative PCR was used to detect the levels of NF-κ B/P65 and P38/MAPK mRNA in rat lung tissue. Western blot was used to detect the protein levels of p-NF-κ B/P65, NF-κ B/P65, P38/MAPK and p-P38/MAPK in rat lung tissue. Results Compared with the model group, the levels of TNF-α, IL-6 and IL-1 β in serum, (PMN) count of neutrophils in bronchoalveolar lavage fluid, wet/dry weight ratio and MDA level of lung tissue, NF-κ B/P65 and P38/MAPK mRNA levels in lung tissue, protein levels of p-NF-κ B/P65, NF-κ B/P65, P38/MAPK and p-P38/MAPK in lung tissue of rats in each dose group were significantly lower than those in model group(P＜0.05), while SOD activity in lung tissue was significantly increased(P＜0.05). The lung histopathology of rats was significantly improved. Conclusion Gegen Qinlian decoction can significantly reduce the level of inflammatory factors and improve the oxidative stress injury and pathological changes of lung tissue in rats with acute lung injury, and its mechanism may be related to the regulation of MAPK/NF-κ B signal pathway.