With the rapid development of aquaculture in recent years, the incidence of aquatic animal diseases, especially fatty liver disease, and its prevalence tended to increase and gradually became a stumbling block of aquaculture industry. Due to lack of effective model to study the pathogenesis, we intend to establish a fatty liver model of zebrafish induced by high-fat diet. In this study, normal diet and 16% high fat diet were fed to 1-month-old zebrafish, respectively. After 14, 30 and 90 days feeding, liver was taken as sample to conduct HE staining, transmission electron microscopy (SEM) and masson staining, and qRT-PCR was used to detect liver tissue genes expression level related to lipogenesis and lipolysis such as DGAT, PPARγ, FAS, SREBP1, CIDE, HSL, ATGL, and through Methanol-chloroform extraction we also detected the liver tissue contents of triglyceride. The result has shown, on the 30 th day, hepatic steatosis has occurred, the lipogenesis genes expression and the contents of triglyceride were significantly increased in high fat diet group. On the 90 th day, high fat diet group of zebrafish liver transmission electron microscopy (sem) and masson staining tissue biopsy showed zebrafish liver fibrosis and liver damage, and liver lipid synthesis genes and triglycerides contents decreased significantly. In conclusion, our high fat diet is able to induce hepatic injury, after 30 d feeding, zebrafish got hepatic steatosis and after 90 d feeding, liver fibrosis happened. Its fat synthetic gene expression level and contents of triglyceride in liver rose first and then fell, which has proven that the fat accumulation induced hepatic injury. The construction of the model remedied the defects of previously-built zebrafish high-fat model and this model will provide a support to study the mechanism of fish nutritional fatty liver disease.