There has been a rapid increase in the prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). NASH is associated with possible progression to liver cirrhosis and cancer. Monosodium glutamate (MSG) treated ICR mice (ICR-MSG) are known to develop obesity, diabetes mellitus, and also NASH-like histopathological changes that are similar to those found in humans. In Ayurvedic medicine, Salacia reticulata has traditionally been used to treat diabetes mellitus and rheumatism. In the present study, we studied the preventive effects of S. reticulata on NAFLD/NASH in ICR-MSG mice. ICR-MSG mice were given S. reticulata extract (SRE) for 8 weeks. Body weight and food intake were determined over time, and at the completion of treatment, blood was drawn and the liver was dissected for determination of biochemical parameters and histopathological examination of the liver cells. Compared with the Normal group, the MSG-Control group showed significant obesity, hyperinsulinemia, abnormal lipid metabolism, marked fatty liver. In contrast, significant suppression of body weight gain and improvement of hyperinsulinemia and abnormal lipid metabolism were observed in the groups treated with SRE. Furthermore, SRE was found to suppress liver hypertrophy and to reduce hepatic triglyceride and total cholesterol levels. Histopathological examination revealed that SRE prevents vacuolar degeneration of hepatocyte by lipid accumulation and suppresses infiltration of inflammatory cells. The above results demonstrated SRE's ability to improve obesity and insulin resistance and to suppress development of fatty liver and infiltration of inflammatory cells, suggesting that SRE is a promising agent for the prevention and treatment of NAFLD/NASH. © 2011, Medical and Pharmaceutical Society for WAKAN-YAKU. All rights reserved.