Aim To study the effect of astragaloside (AS-Ⅳ) in CLP-induced septic mice.Methods C57BL/6 mice were randomly divided into the sham group, CLP group and CLP+ AS-Ⅳ group.Two days before operation, AS-Ⅳ (10 mg·kg-1) solution was intragastrically administered into CLP +AS-Ⅳ group, and the other groups were treated with normal saline.A sepsis model was established by cecal ligation and puncture (CLP).Blood, peritoneal fluid and tissue organs were collected at 6 h and 24 h.Neutrophils of blood were purified by Percoll density gradient.Transwell was used to detect the chemotaxis function of neutrophils.The killing activity of neutrophils was detected by coculture with E.coli.Results The survival rate of AS-Ⅳ-pretreated septic mice significantly increased.The number of neutrophils in peritoneal fluid was enhanced markedly.The number of bacteria in the peritoneal fluid, blood and tissue organs such as liver, lung and kidney significantly decreased after AS-Ⅳ pretreatment.The chemotaxis and killing activity of neutrophils increased significantly in AS-Ⅳ-treated mice (P<0.05).Conclusion Astragaloside displays an immunoprotective effect in CLP-induced septic mice, which is related to the upregulation of CXCR2 expression on neutrophils and the increase of neutrophil antibacterial activity.