Sepsis and its complications, including multiple organ failure are associated with high mortality in patients in intensive care unit. Coagulation abnormalities, such as thrombocytopenia, prolonged clotting time and consumption coagulopathy, occurred in nearly all patients with severe sepsis. Gabexate mesilate (GM), a synthetic serine protease inhibitor, is known to be an anticoagulant by competitively inhibiting activities of thrombin and factor Xa as well as plasmin and plasma kallikrein. Several studies report that GM has protective effects against tissue injury in models of endotoxemia. The aim of this study was to examine whether GM could attenuate organ dysfunction and improve survival rate in an animal model of lipopolysaccharide (LPS)-induced endotoxemia (Tsai et al, 2012). LPS (30 mg/kg over a 4-h intravenous infusion) was administered to male adult Wistar rats (250-300 g). Bacterial LPS (E. coli serotype 0127:B8, L3127) was used in this study. Some of rats received a continuous infusion of GM (10 mg/kg/h for 8.5 h) at 30 min prior to the infusion of LPS as the treatment group. Variables of hemodynamic and biochemistry were measured during the subsequent 6 h after the start of LPS infusion. Parameters of thrombelastography, hemostasis and inflammatory response were also measured, and survival rate was monitored every 30 min during the 8-h experiment. The administration of LPS rats with GM (i) alleviated hypotension, (ii) attenuated the LPS-induced liver and kidney dysfunction, (iii) minimized consumptive coagulopathy displayed by thrombelastography, (iv) attenuated the rises in serum tumor necrosis factor-α, interleukin-6, and plasma thrombin-antithrombin complex as well as plasminogen activator inhibitor-1, (v) reduced neutrophils infiltration score in lung, liver and kidney, and (vi) significantly increased the 8-h survival rate (58.3%), when compared to the LPS group (25.7%, p<0.05). These results suggest that the pre-treatment of LPS rats with GM not only reduces organ injury but also improves survival rate. These protective effects of GM may be attributed to its anti-inflammation and anti-coagulation properties.