Objective To evaluate the role of p38 mitogen-activated protein kinase (p38MAPK)-heat shock protein 27 (HSP27) signaling pathway in attenuation of lipopolysaccharide (LPS)-induced acute lung injury (ALl) by dexmedetomidine in mice.Methods Forty male Kunming mice,aged 2 months,weighing 20-25 g,were equally and randomly divided into 4 groups using a random number table:control group (group C),LPS group,low-dose dexmedetomidine + LPS group (group D1),and high-dose dexmedetomidine + LPS group (group D2).Dexmedetomidine 25 and 50 μg/kg were injected intraperitoneally in D1and D2 groups,respectively,and 1 h later LPS 5 mg/kg was injected intraperitoneally.At 6 h after LPS injection,the left lung was lavaged,and broncho-alveolar lavage fluid (BALF) was collected for determination of concentrations of protein,tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β).The right lung was removed for examination of the pathological changes (under the light microscope) and for detection of expression of phosphorylation of p38MAPK (p-p38MAPK),p38MAPK,phosphorylation of MAPK-activated protein kinase 2 (p-MAPKAPK-2),MAPKAPK-2,phosphorylation of HSP27 (p-HSP27) and HSP27 in lung tissues.The wet to dry lung weight (W/D) ratio was calculated.The ratios of p-p38MAPK/p38MAPK,p-MAPKAPK-2/MAPKAPK-2 and p-HSP27/HSP27 were calculated.Results Compared with group C,the W/D ratio,concentrations of protein,TNF-α and IL-1β in the BALF,and ratios of p-p38MAPK/p38MAPK,p-MAPKAPK-2/MAPKAPK-2 and p-HSP27/HSP27 were significantly increased in group LPS.Compared with group LPS,the W/D ratio,concentrations of protein,TNF-α and IL-1β in the BALF,and ratios of p-p38MAPK/p38MAPK,p-MAPKAPK-2/MAPKAPK-2 and p-HSP27/ HSP27 were significantly decreased in D1 and D2groups.The pathological changes of the lung were significantly reduced in D1 and D2 groups as compared to LPS group.Conclusion Dexmedetomidine attenuates LPS-induced ALI in mice possibly through inhibiting p38MAPK-HSP27 signaling pathway.