Abstract: OBJECTIVE To explore the effect of artemisinin (ART) on improving the sepsis-induced lung injury by regulating macrophage polarization through the PI3K-AKT-mTOR signaling pathway and observe the potential mechanisms. METHODS Totally 128 male C57BL/6 mice, 8 controlled mice and another 120 mice were selected to injected with Staphylococcus aures/Escherichia coli so as to construct the gram-positive bacteria/gram-negative bacteria (G⁺/G-) sepsis models. All mice were treated with ART25mg/kg for gavage and were then randomly divided into the mTOR agonist MHY1485 intervention group, the mTOR inhibitor rapamycin intervention group and the ART group. The wet-dry mass ratio (W/D) of lung tissues, levels of inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), pathologic change of lung tissues and expression levels of PI3K-AKT-mTOR pathway key proteins and macrophage polarization markers-related proteins were detected after the interventions for 24 hours. RESULTS As compared with the sepsis group, ART remarkably improved the lung injury of the mice with sepsis, reduced the levels of TNF-α and IL-6 in serum and BALF, raised the IL-10 level, relieved the lung tissue edema, and improved the pathological injury of lung tissues. ART remarkably inhibited the expressions of M1 type markersinducible nitric oxide synthase(iNOS), TNF-α, promoted the expressions of M2 type markers (Arg-1, CD206) and concurrently increased the expression levels of p-PI3K, p-AKT and p-mTOR proteins(P＜0.05). the mTOR agonist MHY1485 could enhance the above effects of ART, while the mTOR inhibitor RAPA had opposite effects. CONCLUSION ART may promote the M2 type polarization of macrophage through PI3K-AKT-mTOR pathway so as to relieve the sepsis-induced lung injury.