Objective：To study the effects of bisphenol S（BPS）on lipid metabolism in zebrafish with high-fat diet and its potential mechanism. Methods：The effects of BPS in different concentration on lipid deposition in the blood vessels of zebrafish with high-fat diet were studied，and the changes of lipid metabolism-related proteins and genes were detected by ELISA and quantitative RT-PCR. Results：The cholesterol accumulation in the larvae blood vessels was significantly decreased under the exposure of 1 and 10 μg/L BPS（P < 0.01）. When fed with high-fat diet 42 mg/dish，the lipid accumulation in the larvae blood vessels of the BPS exposed group was also significantly decreased（P < 0.01）. The expression level of RXRα protein was significantly reduced in the 100 μg/L BPS exposed group（P < 0.05）. The gene expression of hmgcrα was significantly induced by 10 μg/L BPS exposure（P < 0.05），and the mRNA levels of ldlrα and rxrα were all significantly decreased in the 100 μg/L and 1 000 μg/L BPS exposed group（all P < 0.05）. While the expression of rorα gene was reduced after exposure of 0.1，1.0，100.0 μg/L BPS（all P < 0.05），and it was lower after exposure of 1 000 μg/L BPS（P < 0.01）. Conclusion：The effect of BPS on lipid metabolism of zebrafish larvae was related to the feeding amount of high-fat diet and abnormal expression of lipid metabolism related genes，and its mechanism may be related to rxr/ror signaling pathway.