Objective:The aim of this study was to determine if dexmedetomidine diminishes pulmonary dysfunction by blocking the p38MAPK activation. Methods:A total of 50 adult male Sprague-Dawley rats were assigned to one of five groups. The 0.9% sodium chloride group (Control group), the lipopolysaccharides group(LPS group), The LPS plus dexmedetomidine group (0.2, 1or 5.0 μg/kg per hour)(Dex0.2 group, Dex1 group and Dex5 group). The rats in the LPS plus dexmedetomidine group were injected a loading dose of dexmedetomidine (1 μg/kg per hour intravenous infusion over 10 minutes) followed by LPS administration and dexmedetomidine infusion at different doses (0.2, 1and 5 μg/kg per hour , respectively) until the end of the experiment. Simultaneously, the LPS and control groups received an equal volume of 0.9% sodium chloride (1ml/kg per hour).Western blot was used to detect the expression of phosphorylation of p38MAPK in lung tissues,Additionally we examined the concentration of TNF-α and IL-10 in BALF, the histopathologic changes of lung ,arterial blood gases and the lung water content . Results:Histological, arterial blood gas analyses and the lung water content confirmed that LPS induced significant lung injury. With the administration of LPS, the phospho-p38 MAPK substantially increased immediately. The concentrations of cytokines were also increased. However, dexmedetomidine at the dose of 5.0 μg/kg per hour, but not at 0.2 or 1.0 μg/kg per hour, significantly attenuated the effects of LPS. Conclution: Dexmedetomidine may attenuates LPS-induced acute lung injury via mechanisms involving inhibiting p38MAPK activation.