Abstract: This study was to investigate the regulation of lipopolysaccharides(LPS)-induced sepsis in mice by preadministration of Shenmai injection(SMI)and the therapeutic differences between male and female, female and male mice were randomly grouped by weight, including control group, LPS-induced sepsis model group and SMI administration group. After preadministration of SMI for 14 days, 10 mg/kg LPS were intraperitoneally injected subsequently to induce sepsis. The survival rate of mice, level of serum cytokines and the mRNA expression of proinflammatory cytokines in main tissues were detected to evaluate the impact of SMI on LPS-induced sepsis mice. From the survival rate, which is considered as a gold standard of improvement in sepsis, significant protective effect can be observed after SMI pretreatment in LPS-induced sepsis mice, with a more significant effect shown in the females. Consisting with the serum cytokines levels, SMI significantly inhibited proinflammatory cytokines including IL-6, IL-1β and TNF-α mRNA expression in tissues and the regulation of IL-6 was most significant, which was consistent with the results of ELISA in serum. Moreover, the liver tissue acquired a more evident impact than any other tissues, which fits with the ratio of dry/wet weight. SMI can significantly inhibit inflammatory response by delivery in advance in LPS-induced septic mice, which provides strong evidence for elaborating the mechanism in the treatment of cardiovascular disease-related inflammation and shock.