ObjectiveTo investigate the protective effect and mechanism of arbutin on LPS induced Acute lung injury in mice. Methods SPF BCLB/C mice were randomly divided into control group, model group,arbutin group, and arbutin+PI3K inhibitor group.arbutin group and arbutin+PI3K group were intervened with corresponding drugs respectively; Constructing an ALI model by intranasal instillation of LPS into mice; After modeling for 6 hours, the mice were killed. After staining the lung tissue slices, observe the pathological changes of the lung tissue and evaluate the lung injury score, and calculate the wet to dry weight ratio (W/D); ELISA method was used to determine the levels of TNF-a and IL-6 in serum and bronchoalveolar lavage fluid (BALF); Measure the ROS content, MDA level,and MPO activity in the lungs; Western blot method was used to detect the expression of PI3K/Akt/mTOR pathway related proteins and autophagy related proteins Beclin-1 and LC3II/I. ResultsCompared with the control group, the pathological changes in the lung tissue of model group mice worsened, and the W/D and lung injury scores increased, The levels of IL-6 and TNF-a in BALF and serum was increased, The ROS content, MDA expression and MPO activity in the lungs was increased,the expression of Beclin-1 and LC3II/I in the lungs was increased. The expression of PI3K/Akt/mTOR pathway related proteins in the lungs decreased (P<0.05). Compared with the model group, the pathological changes in the lung tissue of arbutin group mice were alleviated, with a decrease in W/D and lung injury score, The levels of IL-6 and TNF-a in BALF and serum decrease,ROS content, MDA expression and MPO activity in lung were decreased.The expression of PI3K/Akt/mTOR pathway related proteins in the lung was increased, The expression of Beclin-1 and LC3II/I decreased. However, the appeal performance was partially blocked in the arbutin+PI3K group after the administration of LY294002.ConclusionsArbutin regulates autophagy through PI3K/Akt/mTOR pathway to inhibit inflammatory response and oxidative stress in LPS-induced ALI mice, and plays a protective role in LPS-induced ALI.