Genistein is a naturally occurring plant-derived phytoestrogen present in the human diet, and is known to possess anti-cancer, anti-oxidant and anti-osteoporosis effects. Anti-inflammatory activity of genistein has been revealed in animal studies. In this paper, we investigated the anti-inflammatory effect of genistein on non-alcoholic steatohepatitis (NASH) rats induced by high fat diet (HFD), and explored its potential mechanisms. Rats were fed with normal chow diet or HFD for 12 weeks with or without low (4 mg/kg/day body weight) or high (8 mg/kg/day body weight) dose of genistein. Serum levels of aminotransferases, thiobarbituric acid-reactive substances (TBARS), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and transforming growth factor beta (TGF-beta(1)) were measured, hepatic inflammation, liver TBARS, IL-6, TNF-alpha and TGF-beta(1) levels were determined, and proteins involved in mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappa B) pathways were assayed. The results showed that the NASH model rats reproduced typical pathogenetic and histopathological features of NASH in human, and genistein administration improved liver function, slowed down NASH progression, decreased the levels of TBARS, TNF-alpha and IL-6 in serum and liver, as well as inhibited I kappa B-alpha phosphorylation, nuclear translocation of NF-kappa B p65 subunit, and activation of c-Jun N-terminal kinase (JNK). In conclusion, genistein may be a promising drug to inhibit the inflammatory process and prevent liver damage in patients with NASH. (C) 2011 Elsevier B.V. All rights reserved.