To observe the therapeutic effect of 6-shogaol(6-SH) on lipopolysaccharide(LPS)-induced pulmonary edema in the mouse model of acute lung injury(ALI) and investigate the possible mechanism.Methods:Forty specific pathogen free(SPF)-grade Balb/c mice were assigned into control，model，6-SH(100 mg/kg)，and dexamethasone(5 mg/kg) groups by the random number table method，with 10 mice in each group.The mouse model of ALI was established by nasal dripping of LPS，and the control group was dripped with an equal amount of normal saline.Thirty minutes after modeling，mice in corresponding groups were administrated with 6-SH by gavage and dexamethasone by intraperitoneal injection.The control and model groups were administrated with an equal amount of normal saline by gavage.The experiment was ended and samples were collected 24 h later.The wet/dry weight(W/D) ratio of the lung tissue and the lung index were determined.The bronchoalveolar lavage fluid(BALF) was collected to determine the white blood cell count and total protein concentration.Hematoxylin-eosin(HE) staining was employed to observe the pathological changes in the lung tissue，and the pathological scores were calculated.Enzyme-linked immunosorbent assay was employed to determine the levels of tumor necrosis factor-α(TNF-α)，interleukin-1β(IL-1β)，and IL-6 in the supernatant of BALF.Western blotting was employed to determine the expression levels of proteins related to the Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/aquaporin(AQP) signaling pathway in the lung tissue.Results:Compared with the control group，the model group showed obvious lung injury，increased pathological scores，lung index，W/D ratio，leukocyte count，total protein concentration，and levels of TNF-α，IL-1β，and IL-6(P<0.01).Compared with the model group，6-SH decreased the W/D ratio，lung index，leukocyte count，total protein concentration，and levels of TNF-α，IL-1β，and IL-6，up-regulated expression levels of AQP1 and AQP5(P<0.01)，and down-regulated expression levels of TLR4，MyD88，NF-κB p65，and p-NF-κB p65(P<0.01 or P<0.05).Conclusion:6-SH may exert the anti-inflammatory effect and improve the water-liquid metabolism and transport in the lung tissue by modulating the TLR4/NF-κB/AQP signaling pathway to alleviate the pulmonary edema in ALI mice.