Previously, we demonstrated that alpha-iso-cubebenol, a natural compound isolated from the fruits of Schisandra chinensis, strongly enhances therapeutic efficacy against cecal ligation and puncture challenge-induced sepsis. In this study, we found that alpha-iso-cubebenol stimulated calcium increase and degranulation in human neutrophils. alpha-Iso-cubebenol also strongly induced neutrophil chemotaxis, which was completely blocked by a CXCR2 antagonist, SB225002. The increased survival rate by alpha-iso-cubebenol was also significantly attenuated by SB225002. Taken together, the results indicate that alpha-iso-cubebenol-induced anti-septic activity was mediated by CXCR2, suggesting CXCR2 as an important target for the regulation of sepsis and inflammation. (C) 2013 Elsevier Inc. All rights reserved.