Propofol, an anesthetic drug, has been shown to exhibit antioxidant and anti-inflammatory properties in vitro and in vivo. Hypercoagulopathy is a common clinical feature of sepsis, but the effects of propofol on the coagulation system in septic conditions are unclear. Using the gel-based comparative proteomic approach, together with Western blot analysis, ELISA, antithrombin III activity assay, and blood coagulation test, the effect of propofol on serumproteomic profiles in endotoxemic ratswas examined.Weidentified that serumplatelet factor-4 (PF4), an endogenous pro-coagulant, was up-regulated in LPS-challenged rats (pb0.001). Endotoxemia also resulted in hypercoagulopathy as evidenced by the shortening of thromboplastin time and thrombin time. Administration of propofol attenuated LPS-stimulated PF4 release and partially reversed the effect of LPS on thromboplastin time (p=0.0012) and thrombin time (p=0.0072).We demonstrated that propofol reduces serum levels of PF4 and partially corrects the hypercoagulopathy associated with endotoxemia in rats.