OBJECTIVE： To investigate the effects of dexmedetomidine combined with mild hypothermia on the levels of High mobility group box 1 protein （HMGB1）， Toll like receptor 4 （TLR4） and Triggering receptor expressed on myeloid cells 1 （Trem-1） in lung tissues of sepsis model rats. METHODS： Totally 100 SD rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， dexmedetomidine group （2 μg/kg）， mild hypothermia group （normal saline+anal temperature 32-35 ℃ caused by whole body spraying of cold water） and combination group （dexmedetomidine 2 μg/kg+anal temperature 32-35 ℃ caused by whole body spraying of cold water）， with 20 rats in each group. Except that sham operation group received sham operation， sepsis model was induced in other groups. After ligation and incision， the corresponding drugs were pumped into the jugular vein and the corresponding body temperature was maintained. Plasma samples were collected 6 h after operation. Interleukin 1 （IL-1）， IL-6， tumor necrosis factor α （TNF-α） were determined by ELISA. The lung wet mass/dry mass ratio （W/D） was calculated by weighing the mass. Lung tissue sections were observed by HE staining， and lung injury scores were scored. The activity of MPO in lung tissue was determined by immunoturbidimetry. The expression of HMGB1，TLR4 and Trem-1 protein was determined by Western blot. RESULTS： Compared with sham operation group， the contents of IL-1， IL-6 and TNF-α， W/D， lung injury score， MPO activity， the protein expression of HMGB1， TLR4 and Trem-1 were increased significantly， with statistical significance （P＜0.05）； lung tissue section showed that alveolar wall was obviously thickened； a large number of inflammatory cells infiltrated； blood vessels were obviously dilated and congested. Compared with model group， above indexes of rats in dexmedetomidine group， mild hypothermia group and combination group were decreased significantly， with statistical significance （P＜0.05）； the degree of pathological changes in lung tissue was significantly reduced. Compared with dexmedetomidine group and mild hypothermia group， above indexes of combination group were decreased more significantly， with statistical significance （P＜0.05）. Alveolar walls were thickened， inflammatory cell infiltration was relieved significantly and no vascular diatation and congestion was found. CONCLUSIONS： Dexmedetomidine combined with mild hypothermia can significantly improve lung injury in sepsis model rats， and down-regulate the protein expression of HMGB1， TLR4 and Trem-1. Therapeutic efficacy of combination therapy is better than single therapy.