OBJECTIVE To study the improvement effects and mechanism of gentian iridoids （GI）on lipid accumulation and inflammation in non -alcoholic fatty liver disease （NAFLD）model. METHODS Human hepatoma HepG 2 cells induced by free fatty acids（0.5 mmol/L）were selected as NAFLD cell models . The effects of GI at different concentrations （0.125，0.25，0.5，1，2，4 mg/mL）on HepG 2 cell viability were investigated . HepG2 cells were divided into control group ，model group and low ，medium and high concentration groups of GI （0.25，0.5 and 1 mg/mL）. Except for control group ，0.5 mmol/L free fatty acid was added in other groups for modeling .After 24 h of culture ，the formation of lipid droplets was observed in HepG 2 cells；the content of triglyceride（TG）was detected . The levels of aspartate aminotransferase （AST），alanine aminotransferase （ALT）and inflammation indexes [interleukin-1 β（IL-1 β），IL-6，tumor necrosis factor α（TNF-α）] in cell supernatant were determined . The mRNA expressions of sterol -regulatory element binding protein （SREBP-1c）and fatty acid synthase （FAS）as well as the expression of nuclear factor -κB（NF-κB）related proteins [NF-κB inhibitor protein α（IκBα），NF-κB，phosphorylated NF -κB（p-NF-κB）] were also detected . RESULTS After treated with different concentrations of GI ，the cell viability of HepG 2 cells was improved significantly（P＜0.01）. Compared with model group ，the number of red lipid droplets in the cells of each concentration group of GI was significantly reduced ，the nuclear atrophy was not obvious ，and the size was normal ；the content of TG （except for low concentration group ），and the levels of ALT ，AST，IL-1β，IL-6（except for low concentration group ）and TNF - α in cell supernatant were all decreased significantly ；mRNA expression of SREBP -1c and FAS and the phosphorylation level of NF -κB were also decreased significantly （P＜0.05 or P＜0.01）；the protein expression of I κBα was increased significantly （P＜0.01）. CONCLUSIONS GI can reduce the lipid accumulation and inflammatory response of NAFLD cell model induced by free fatty acids，and its mechanism may be related to the inhibition of SREBP-1c/FAS and NF -κB signaling pathway .