Objective:To establish a stable and reliable model of zebrafish hyperlipidemia and evaluate the effect of high cholesterol diet on the lipid metabolism in zebrafish larvae. Methods:Zebrafish larvae after five days post fertilization(5dpf)were randomly divided into two groups:normal feed group with dry powder of pure egg yolk,and high cholesterol feed model group with different percentages of cholesterol added to pure egg yolk. After 10 days,the evaluation was carried out by microscopy and detecting the physiological and biochemical indicators in the zebrafish larvae. Results:Confocal microscopy showed that the lipid deposition in caudal artery of juvenile fishes in high cholesterol diet model group was significantly higher than that in common diet group(P < 0.05),and the lipid deposition in caudal artery of juvenile fishes increased with the increase of cholesterol content in diet. When the feed intake of the 5% high cholesterol diet group increased,the lipid deposition in blood vessel increased significantly at the beginning(P < 0.05)and subsequently stabilized gradually,but the survival rate of juvenile fishes decreased significantly(P < 0.05). The body width of fish larvae in the 5% high cholesterol diet group was significantly larger than that in common diet group(P < 0.01),but no significant differences in body length were observed between the two groups(P > 0.05). The levels of total cholesterol(TC)and total triglyceride(TG)in juvenile fishes fed with 5% high cholesterol diet were both significantly higher than those fed with normal diet(P < 0.01),and the levels of LDL-C were also significantly higher(P <0.05). Conclusion:Feeding 5% high cholesterol diet for 10 days could induce the occurrence of hyperlipidemia in zebrafish. Increasing the percentage of cholesterol in diet or increasing the dosage of high cholesterol properly could accelerate the establishment of hyperlipidemia model.