Objective To explore the effect of leukotriene B4 receptor 1 antagonist(U-75302) on sepsis in mice. Methods Experimental sepsis model was induced by cecal ligation and puncture (CLP). 18 male C57BL/6 mice were randomly divided into sham group (n=6), CLP group (n=6) and CLP + U-75302 intraperitoneally group (n=6) completely. Mice blood, peritoneal lavage fluid, liver and lung were harvested 24 h after operation to determinate blood and peritoneal cavity bacterial burden, liver and lung pathological detection respectively. 24 male C57BL/6 mice were randomly divided into sham group (n=8), CLP group (n=8) and CLP + U-75302 intraperitoneally group (n=8). Survival was recorded for 7 days. Results CLP-operated C57BL/6 mice treated with U-75302 intraperitoneally showed lower bacterial burden compared with CLP group (p<0.01), peripheral blood bacterial burden and peritoneal lavage fluid bacterial burden reduced by 74% and 68% respectively. The injury score of liver and lung were reduced by 62% and 47% respectively compared with CLP group (p<0.01). The survival rate increased by 16% compared with CLP group (p<0.05). Conclusions leukotriene B4 receptor 1 antagonist(U-75302) could protect mice from sepsis, but the mechanism remains to be discussed.