〔Abstract〕 To investigate the role of endoplasmic reticulum stress in the occurrence and development of fatty liver induced by high fat. Methods In the high-fat Drosophila model , the high-fat group was fed with high-fat medium , while the control group was fed with normal medium; in the mouse fatty liver model , the high-fat group was fed with high-fat diet , and the control group was fed with normal diet; in the HepG2 cell steatosis model , the high-fat group was induced by palmitic acid (PA) , and the control group was cultured with DMEM . The fat body size of the third instar larvae of Drosophila melanogaster was photographed . Steatosis in mice liver and HepG2 cells was observed by H&E and Oil Red staining. The expression levels of ATF6 , Bip and CHOP in the third instar lar- vae , liver tissues of mice and HepG2 cells were analyzed by quantitative real-time polymerase chain reaction (qPCR) and Western blot. Results In Drosophila model , fat body and fat storage were obviously increased in high fat fed flies when compared with control group . The formation of liver fat droplets and cells vacuolation were confirmed by H&E and Oil Red staining in mice livers fed with high fat and HepG2 cells with palmitic acid treat- ment. The expression levels of ATF6 , Bip and CHOP were significantly increased in third instar larvae and mice livers fed with high fat and palmitic acid treated HepG2 cells with palmitic acid treatment. Conclusion High fat may induce the occurrence and development of hepatic steatosis by activating endoplasmic reticulum stress .