Non-alcoholic fatty liver disease (NAFLD) is considered a worldwide epidemic defined as the accumulation of excessive fat in the liver in the absence of excessive drinking of alcohol. Its prevalence in the Middle East ranges between 20 and 30 %. We designed this study to evaluate the preventive effect of both metformin and losartan on NAFLD in rats. We induced NAFLD by high fat diet and fructose in drinking water for 8 weeks. Twenty four rats were used in this study and randomly divided into 4 groups; control group, high fat diet group, high fat diet with metformin group and high fat diet with losartan group. Blood samples were used for detection of liver enzymes and lipid profile assessment. Paraffin and frozen liver sections were done. Metformin and losartan significantly prevented the increase in the serum levels of liver enzymes and the lipid profile induced by NAFLD in rats. Also, they partially preserved the hepatic architecture.