AIM: To evaluate the prophylactic properties of integrin CD18-βA peptide in a murine model of abdominal polymicrobial peritonitis and sepsis. METHODS: Bacterial sepsis was induced in Institute of Cancer Research (ICR) mice by cecal ligation and puncture (CLP) surgery. Inflicted mice were then injected with either sterile saline or CD18-βA peptide intraperitoneally at 2 h after surgery, and were sacrificed at 12 and 24 h after surgery. Blood samples were immediately collected, and analyzed for endotoxin activity and tumor necrosis factor (TNF)-α and interleukin (IL)-6. Lungs and liver were studied for CD45+ leukocyte and CD3 mRNA content. Pulmonary expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM) and E-selectin was also determined. RESULTS: Intraperitoneal injection of CD18-βA peptide significantly suppressed circulating endotoxin activity ( P < 0.01) at 24 h, as well as serum levels of TNF-α ( P < 0.05 at 12 and 24 h) and IL-6 ( P < 0.01 at 12 h, P < 0.05 at 24 h) in CLP-inflicted mice. CD18-βA peptide also abrogated leukocyte infiltration into liver and lungs as unveiled by reduced CD45+ leukocyte and CD3 mRNA contents. Furthermore, the peptide significantly reduced pulmonary expression of VCAM ( P < 0.01 at 12 h, P < 0.001 at 24 h), E-selectin ( P < 0.01 at 12 and 24 h), and ICAM-1 ( P < 0.01 at 12 h, P < 0.001 at 24 h). These actions of CD18-βA peptide collectively protected septic mice against lethality ( P < 0.01). CONCLUSION: CD18-βA peptide is a potent endotoxin antagonist that can protect surgical patients against sepsis-associated lethality.