AIM: To investigate the effects of antithrombin III (AT III) injection via the portal vein in acute liver failure. METHODS: Thirty rats were intraperitoneally challenged with lipopolysaccharide (LPS) and D-galactosamine (GaIN) and divided into three groups: a control group; a group injected with AT III via the tail vein; and a group injected with AT M via the portal vein. AT III (50 U/kg body weight) was administrated 1 h after challenge with LPS and GaIN. Serum levels of inflammatory cytokines and fibrin degradation products, hepatic fibrin deposition, and hepatic mRNA expression of hypoxia-related genes were analyzed. RESULTS: Serum levels of alanine aminotransferase, tumor necrosis factor-a and interleukin-6 decreased significantly following portal vein AT III injection compared with tail vein injection, and control rats. Portal vein AT M injection reduced liver cell destruction and decreased hepatic fibrin deposition. This treatment also significantly reduced hepatic mRNA expression of lactate dehydrogenase and heme oxygenase-1. CONCLUSION: A clinically acceptable dose of AT M injection into the portal vein suppressed liver damage, probably through its enhanced anticoagulant and anti-inflammatory activities. (C) 2012 Baishideng. All rights reserved.