Objective: To investigate the protective effects and mechanism of naringenin (NAR) on high-fat， high-sugar induced mice with non-alcoholic fatty liver disease (NAFLD). Methods: Mice were fed with a high-fat and high-fructose diet to establish a NAFLD model， orally administration of naringenin was performed during the experiment. After 9 weeks， the body weight， epididymis fat weight and liver weight were observed， levels of the serum and liver triglyceride， serum ALT， AST were measured； Levels of hepatic inflammatory factors and serum lipopolysaccharides (LPS) was determined by ELISA， the pathological changes of liver tissues in mice were observed， and the localization of bacteria derived lipopolysaccharides in the liver flora was determined using anti- LPS obtained from Escherichia coli. Results: Naringenin significantly reduced the increased body mass (P＜0.001) and liver weight of NAFLD mice (P＜0.01) induced by HFFD， decrease the serum and hepatic TG level (P＜0.05)， the serum ALT (P＜0.05) and AST levels (P＜0.01)， and improved the liver steatosis and lipid accumulation. Meanwhile， naringenin reduce the localization of bacteria derived LPS (P＜0.01) in mice liver and intestinal permeability. Conclusion: This study initially reveals that naringenin may reduce the bacteria-derived LPS location in mice liver by reducing intestinal permeability， thereby reducing liver inflammation， and alleviating the high-fat and high-fructose induced non-alcoholic fatty liver diseases in mice.