Objective To study the effect of dexmedetomidine hydrochloride (Dex) on lipopolysaccharide (LPS) induced inflammatory response in Kupffer cells. Methods Healthy male SD rats were selected for isolation and culture of liver Kupffer cells. The cells were randomly divided into 6 groups: normal group, model group, experimental-L group, experimental-H group, combined group and control group. The normal group was cultured routinely, model group was cultured with 1μg·m L-1 LPS solution 3 h, experimental-L, experimental-H group were cultured respectively with 0. 01 μmol·L-1 or 1 μmol·L-1 Dex 24 h + 1 μg·m L-1 LPS solution 3 h, combined group was cultured with 1μmol·L-1 Dex + 100 μmol·L-1 yohimbine hydrochloride (α2 adrenergicreceptor antagonist) 24 h + 1 μg·m L-1 LPS 3 h, control group was cultured with 100 μmol·L-1 yohimbine hydrochloride 24 h. The survival rate of Kupffer cells was determined by MTT. The contents of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the supernatant of Kupffer cells were determined by enzyme linked immunosorbent assay. Results After disposal, the survival rates of Kupffer cells in normal group, model group, experimental-L group, experimental-H group, combined group and control group were respectively (100. 00 ± 0. 00) ％, (56. 35 ± 4. 21) ％, (64. 78 ± 4. 37) ％, (83. 84 ± 5. 16) ％, (57. 03 ± 4. 09) ％ and (54. 58 ± 3. 95) ％. The TNF-αin the 6 groups were respectively (1. 19 ± 0. 16) , (57. 36 ± 7. 23) , (48. 27 ± 5. 58) , (7. 64 ± 0. 92) , (56. 98 ± 7. 05) and (58. 03 ± 7. 34) ng ·m L-1; the IL-6 in the 6 groups were respectively (47. 38 ± 6. 05) , (289. 49 ± 27. 83) , (231. 17 ± 22. 58) , (85. 35 ± 8. 23) , (287. 96 ± 26. 45) and (291. 43 ± 28. 04) pg·m L-1. Comparison between model group and normal group, the differences of the factors were significant (all P < 0. 05) ; comparison between two dose experimental groups and model group, the differences of the factors were significant (all P < 0. 05) ; comparison between combined group and control group with two dose experimental groups, the differences of the factors were significant (all P < 0. 05) . Conclusion Dex can reduce the activity of LPS induced Kupffer cells in a dose-dependent manner, inhibit oxidative stress injury and inflammatory response induced by Kupffer cells, which may be related to the agitation ofα2 adrenalic receptor. Yohimbine has antagonistic effect on its therapeutic effect.