ABSTRACT: PURPOSE:This study aimed to study the protective effects and mechanism of Blue Honeysuckle (BH) extracts (Berries of Lonicera caerulea L.) on non-alcoholic fatty liver disease (NAFLD) and obesity risk factors in a high fat-diet (HFD) model. METHODS:Animals adapted to HFD were selected after 1 week of adaption period and divided into 6 groups (8 mice in each group; 40 HFD-fed mice and 8 normal fat pellet diet (NFD)-fed mice). After the end of 12 weeks of continuous oral administrations of 3 different dosages of BH extract, 400, 200 and 100 mg/kg, or metformin 250 mg/kg, dissolved in a volume of 10 mL/kg distilled water, the hepatoprotective, hypolipidemic, hypoglycemic, nephroprotective, and anti-obesity effects were analyzed. RESULTS:The BH extract improved fat density and mass, adipocyte histopathology, hepatocyte hypertrophy, hepatic enzyme activity, lipid metabolism, and related gene expression including ACC1, AMPK ?1 and AMPK ?2 in hepatic tissue, leptin, UCP2, adiponectin, C/EBP ?, C/EBP? and SREBP1c in adipose tissue. Especially, 200 mg/kg of BH extract constantly improved NAFLD and obesity risk factors through AMPK upregulation-mediated hepatic glucose enzyme activity, lipid metabolism-related gene expression, and activation of the antioxidant defense system, to a level comparable to that of metformin 250 mg/kg in HFD-fed mice. CONCLUSION:BH extract has the potential to reduce the risk factors associated with obesity, in addition to the remarkable effect of preventing NAFLD. Future research will need to be done to determine whether these results are consistent in human studies.