Aim of this study was to investigate that effect of etanercept administration on the concentrations of cytokines, fibrinogen, antithrombin, 13,14-dihydro-15-keto-prostaglandin F-2 alpha and biochemical values in the endotoxemia. A totally male 126 Sprague Dawley rats were divided 3 equal groups; lipopolysaccharide (4 mg, IP), etanercept (8 mg/kg, IP) and lipopolysaccharide + etanercept were administered to Group 1, 2, and 3, respectively. Blood samples were collected at 0, 1, 2, 4, 8, 12 and 24th hours after treatments. Serum tumor necrosis factor-a, interleukin-1 beta, interleukin-10 and plasma 13,14-dihydro-15-keto-prostaglandin F-2 alpha levels were measured with ELISA reader, while antithrombin and fibrinogen levels were measured with coagulometer. Serum biochemical parameters were determined with auto-analyzer. Etanercept had irregular effect on the fibrinogen levels and it increased PGM, alkaline phosphatase and alanine aminotransferase activities. Lipopolysaccharide increased cytokines, PGM, fibrinogen, organ damage markers and triglyceride levels, and it had irregular effect on the antithrombin levels. Increased cytokines, PGM and fibrinogen levels were determined in lipopolysaccharide + etanercept group, but irregular changes were observed in antithrombin levels. Etanercept exactly depressed the increased creatine kinase-MB level and relatively depressed the increased tumor necrosis factor-a while it extended the presence of tumor necrosis factor-a, and it increased the elevated interleukin-10 levels by lipopolysaccharide. In conclusion, when protective effect of etanercept on the heart and increasing effect on the interleukin-10 levels in the endotoxennia is considered, single dose etanercept may be beneficial in the veterinary medicine.