OBJECTIVE： To study the effect and its mechanism of dexmedetomidine （Dex） on inflammatory response in septic mice. METHODS： Mice were randomly divided into normal control group， model group， miR-146a inhibitor （50 mg/kg）+Dex （50 μg/kg） group， Dex low-dose， medium-dose， high-dose groups （10， 30， 50 μg/kg）， 10 in each group. Except for normal control group， other groups were intraperitoneally injected lipopolysaccharide to induce septic models， intraperitoneally injected relevant medicines after 0.5 h. After drug intervention for 6 h， miR-146a expression， IRAK1 and TRAF6 mRNA expressions in peripheral blood mononuclear cells in each group were detected by real-time fluorescence quantitative polymerase chain reaction method. IRAK1， TRAF6 protein expressions in peripheral blood mononuclear cells in each group were detected by Western blot method. TNF-α， IL-6 levels in serum were detected by enzyme-linked immunosorbent method. RESULTS： Compared with normal control group， miR-146a expression， TNF-α and IL-6 levels， IRAK1， TRAF6 mRNA and protein expressions in peripheral blood mononuclear cells in model group were increased （P＜0.01）. Compared with model group， miR-146a expression in peripheral blood mononuclear cells in Dex medium-dose， high-dose groups were increased； TNF-α and IL-6 levels， IRAK1， TRAF6 protein expressions were decreased （P＜0.05 or P＜0.01）； while IRAK1， TRAF6 mRNA expressions changed less obviously （P＞0.05）. Compared with Dex high-dose group， miR-146a expression， in peripheral blood mononuclear cells in miR-146a inhibitor+Dex group was decreased； TNF-α and IL-6 levels， IRAK1， TRAF6 protein expressions were increased （P＜0.05 or P＜0.01）； while IRAK1， TRAF6 mRNA expressions changed less obviously （P＞0.05）. CONCLUSIONS： Dex can inhibit the inflammatory response in septic mice. The mechanism may associate with inducing miR-146a expression and inhibiting the 2 important adaptor proteins IRAK1， TRAF6 expressions in Toll-like receptor 4/nuclear factor-κB pathway.