The obesity epidemic is in the United States and world for past two decades. There is a link between obesity and chronic diseases development such as diabetes, cardiovascular disease, certain types of cancers and liver including non-alcoholic fatty liver disease (NAFLD). Obesity has a significant impact on the metabolic profiles for a variety of cellular-tissue-organ levels in animals and humans. Previously, we reported that obesity caused 1) a significant oxidative/nitrosative stress and these changes may contribute to the development of NAFLD and 2) a significant increase NAFLD and 3) feeding soy protein isolate (SPI) reduced NAFLD. The mechanism of SPI protection on NAFLD is less known. In current study, we hypothesize that SPI diet will reduce the development of NAFLD caused by obesity in part by changing oxidative stress and methylation. After one week of acclimation, five weeks old female lean and obese Zucker rats (n = 8/group) were randomly fed AIN-93-G diet with either casein (CAS as control) or SPI as source of protein for 22 weeks. Rats were weighted twice per week. Liver sample metabolites concentrations were measured using HPLC with Electrochemical Detection and LC-MS.