Objective To investigate whether dexmedetomidine alleviates lipopolysaccharide (LPS)-induced acute lung injury(ALI) through alpha-7 nicotinic acetylcholine receptor (α7nAChR) mediated TLR4/NF-κB pathways. Methods Twenty-four Wistar rats were randomly divided into 4 groups: control group (n=6), acute lung injury group (n=6), dexmedetomidine treatment group (n=6), and α7nAChR inhibitor α-BGT group (n=6). After anesthesia, rats in the control group were intraperitoneally injected with normal saline to serve as normal control; the rest rats all received LPS (10 mg/kg) via a femoral vein to induce the ALI model. For the dexmedetomidine treatment group, rats were continuously injected with dexmedetomidine (5 μg/kg per hour) via the femoral vein immediately after LPS administration. For the α7nAChR inhibitor α-BGT group, rats received 1 μg/kg α-BGT half an hour before dexmedetomidine administration as the dexmedetomidine treatment group. The rats were sacrificed 12 hours after LPS injection to collect the blood and lung tissues. Histology of the lungs was examined with HE staining. The lung injury score was calculated. In the blood sample, PaO₂, HCO₃^–, Lac, W/D, MPO activity were measured. The number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) were measured, and the concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10 in serum were measured by ELISA. The protein expression of α7nAChR, TLR4, p-NF-κB were determined by Western blotting. Results Compared with the control group, LPS induced marked lung histological injury, which was less pronounced in the dexmedetomidine treatment group. Compared with the control group, the levels of PaO₂ and HCO₃^– were decreased, Lac, W/D, TNF-α, IL-6, IL-10, MPO, the total number of cells, neutrophils, and macrophages were increased in the acute lung injury group (P<0.01). Compared with the acute lung injury group, PaO₂, HCO₃^– and IL-10 were increased, and Lac, W/D, TNF-α, IL-6, MPO, the total number of cells, neutrophils, and macrophages were decreased in the dexmedetomidine treatment group (P<0.01). Compared with the control group, the protein levels of α7nAChR, TLR4, p-NF-κB were increased in the acute lung injury group (P<0.01). Compared with the acute lung injury group, the protein levels of α7nAChR was increased, and TLR4, p-NF-κB were decreased in the dexmedetomidine treatment group (P<0.01).However, the effect of dexmedetomidine was reversed by the α7nAChR inhibitor α-BGT. Conclusion Dexmedetomidine may reduce LPS-induced ALI through α7nAChR mediated TLR4/NF-κB pathways.