Introduction: Non-alcoholic fatty liver disease (NAFLD), along with obesity, diabetes, lipid dysregulation, and cardiovascular disease, define the metabolic syndrome. This has reached epidemic proportions in the Unites States, affecting ˜30% of the population, and is one of the major disease states with an increasingprevalence. NAFLD ranges from simple steatosis to inflammatory, non-alcoholic, steatohepatitis (NASH), which can lead to fibrosis, cirrhosis, and eventual hepatocellular carcinoma (HCC). The long term effects of a high protein diet on the pathophysiology of NAFLD have not been previously examined. Aims: To examine the effects of high protein diets on body weight, composition, feeding behavior, orexigenic and anorexigenic metabolic hormones, visceral and liver fat composition. Methods: Male mice (C57Bl/6) were randomized into either three eucaloric (3.85 kcal/g) diet groups: Standard (10% fat, 70% CHO and 20% protein) (n=10), high fat ( 45% fat, 35% CHO and 20% protein kcal) (n=14) and high protein diet (calories: 10% fat, 30% carbohydrate and 60% protein) (n=8) for 12 weeks. Body wt, hepatic, visceral and peripheral fat measured bi-weekly using quantitative nuclear magnetic resonance. Feeding behavior microstructure was analyzed using the BioDAQ episodic food intake monitor for mice. Plasma levels of active ghrelin, GLP-1, PYY, insulin, glucagon, and leptin were analyzed both fasting and postprandial. Hepatic and visceral organs were analyzed by immunohistochemistry, and gene expression examined by qRT-PCR. Results: Mice on a HFD had a significantly greater amount of epididymal and hepatic fat whereas, mice on the HPD had a significantly lower amount of hepatic fat compared to either the standard or HFD. Fasting and postprandial leptin content was significant reduced in HPD whereas active-ghrelin was increased in HFD compared to standard diet. Immunohistochemistry revealed a significant reduction in hepatic steatosis and visceral fat, and de novo lipogenic and beta oxidative pathways were diminished by qRT-PCR. Conclusion: This is the first study to demonstrate that hepatic steatosis can be ameliorated by use of a high protein diet. These results establish the potential novel role of a HPD in the treatment of NAFLD and NASH perhaps through the release of gastrointestinal hormones.