Objective To explore molecular mechanisms of dexmedetomidine(Dex)function as protec-tive effect on acute lung injury(ALI). Methods Hemorrhagic shock ALI rat model was constructed and divided into 6 groups at random:C group,control group;A group,ALI;G,ALI rat groups were treated with 5μg/kg;I1 group,ALI+PDTC(200 mg/kg);I2 group,ALI+STA-21(100 mg/kg). After 12 h modeled,all rats were anes-thetized and killed,and BALF was collected and the concentrations of TNF-α,IL-6,IL-1β,IL-4 were deter-mined using ELISA. HE staining to observe the morphology of lung tissue. Expression of NF-κB,STAT-3,p-STAT-3 proteins were determined using immunohistochemistry or Western blot. Results In A group,the structure of lung tissue were strongly destroyed ,a large number of neutrophils invasion and red blood cells leakage was found;lung tissue structure in G,I1 and I2 groups were gross integrity. The concentrations of TNF-α,IL-6,IL-1β,IL-4 in A group were significantly higher than C group(P<0.05). The concentrations of TNF-α,IL-6,IL-1β,IL-4 in G group,I1 group and I2 group was significantly lower than A group(P<0.05). The levels of NF-κB and p-STAT-3 protein in A group were obvious enhanced(P < 0.05)compared with G group,I1 group,I2 group,respectively. Conclusion Dex inhibited inflammatory to exert lung protective effect via inhibiting NF-κB,STAT-3 activation-induced by ALI.