The effects of decursinol on various models of sepsis were investigated. Intra-peritoneal pretreatment of mice with various doses of decursinol (1∼100 mg/kg) effectively suppressed lethality induced in three mouse models of experimental sepsis, i.e., lipopolysaccharide (LPS)/D-galactosamine (GalN), high-dose LPS (20 mg/kg), and cecal ligation and puncture (CLP). Intra-peritoneal pretreatment of mice with decursinol (50 mg/kg) markedly enhanced the LPS/GalN-induced increase of plasma interleukin-10 (IL-10) levels, without affecting plasma TNF-Ձ, IL-6 and IL-12 levels. These results suggest that decursinol could be effective for prevention or treatment of sepsis.