Objective The purpose of this study was to establish and evaluate a mouse model of sepsis for studying the mechanism of sepsis and development of anti-inflammatory drugs. Methods The sepsis in mice was induced by cecal ligation and puncture (CLP). The survival rates, microbial load, liver and kidney damages, cytokines and pathological changes were detected to evaluate the mouse models. Results The death of mice was closely related with the ligated sites. The mice with 50% cecal ligation displayed about 40% of 12-day survival rate, however, all the mice with 75% cecum ligation died within 4 days (P<0.01). Compared with the sham surgery group, the mice with 50% cecal ligation had a high microbial load in the blood and abdominal cavity. Leukopenia was also emerged (P<0.001). CLP mice demonstrated elevated levels of serum ALT, AST and BUN (P<0.01). The levels of IL1α, IL6, IL10, MIP1α, MIP1β, and TNFα were increased a lot. The liver and lung showed obvious pathological injury at 48 h post CLP. Conclusions The established mouse model of CLP shows typical characteristics of sepsis and is an ideal tool for further study of anti-inflammatory drugs.