Abstract: OBJECTIVE To investigate the effects of isomangiferin (ISO) on high-fat diet induced nonalcoholic fatty liver disease in rats. METHODS Animals were randomly divided into 4 groups: control group， model group which received high-fat diet， ISO group which received high-fat diet+ISO (20， 40 mg/kg). The animals were fed with a high-fat diet for six weeks. The control rats consumed a standard diet at the same time. From the fifth week， ISO group rats were treated with ISO (20，40 mg/kg) for two weeks. Alanine transaminase (ALT)， aspartate transaminase (AST)， serum triglyceride (TG)， serum cholesterol (TC) and cell supernatant cytokines (IL-1β， IL-6， TNF-α) in serum were detected. Liver pathological changes were detected by HE， and liver Sirt1/NF-κB signal pathway was detected by Western blot. In vitro cells were treated with palmitic acid to induce liver L02 cell injury model， to detect cell viability， the levels of IL-1β， IL-6 and TNF-α in cell supernatant， and Sirt1/NF-κB signaling pathway protein expression. RESULTS The results of in vivo experiments showed that， ISO significantly reduced the levels of ALT， AST， TG， TC， serum and cell supernatant cytokines (IL-1β， IL-6， TNF-α) and improved liver histopathological changes. ISO also increased the expression of Sirt1 protein and decrease the expression of NF-κB signaling pathway protein in the liver. The results of in vitro experiments showed that ISO significantly increased L02 cell viability， reduced the level of inflammatory factors in cell supernatant， increased the expression of Sirt1 protein and decreased the expression of NF-κB signaling pathway protein in L02 cells. CONCLUSION These results suggest that ISO is beneficial to nonalcoholic fatty liver disease via Sirt1/NF-κB pathway.