【Abstract】Objective To study the effects of sodium butyrate on toll like receptor 4 (TLR4) liver injury of endotoxemia mice. Methods Mice were randomly received a single intratracheal instillation with either normal saline (control cohort) or 4mg/kg LPS (LPS cohort). Mice from LPS cohort were subsequently assigned to 5 groups including model group administered with normal saline, the control group with dexamethasone-21-acetate at 10mg/kg, the low-dose group, middle-group and high-dose group respectively received sodium butyrate solution at a concentration of 0.4mg/kg, 2mg/kg and 10 mg/kg. The histological change of liver was examined by hematoxilin and eosin and TUNEL. Levels of alanine aminotransferase (ALT), aspartate aminotransferase（AST）and alkaline phosphatase (ALP) in the serum were determined by spectrophotometry. Expression levels of TLR4, nuclear factor-κB (NF-КB), and tumor necrosis factor-α(TNF-α) were measured by real-time PCR and enzyme linked immunosorbent assay (ELISA). Results Results showed that the sodium butyrate treatment result in a decrease of the liver damage in the septic mice. Compared with model group, levels of ALT, AST and ALP of serum in sodium butyrate highdose group reduced 54.03%（P<0.01）, 61.72%（P<0.01）and 46.15%（P<0.01）, respectively. Meanwhile, real-tmie PCR showed that levels of TLR4, NF-КB and TNF-α reduced 61.48%(P＜0.01), 64.51%(P＜0.01) and 50.34%(P＜0.01). Results of ELISA showed that levels of TLR4, NF-КB and TNF-αreduced 57.82%(P＜0.01), 46.17%(P＜0.01) and 61.5% (P＜0.01), respectively. Conclusions Administration of sodium butyrate can result in a protective effects on liver damage of endotoxemia mic maybe through downregulation of TLR4 expression.