Abstract: OBJECTIVE Using zebrafish model to explore the toxic of Psoralen on liver METHODS Recording the number of the survival and the death of zebrafish larval in different concertrations of ethanol extract and water extract， to calculate the mortality and evaluate their toxicity. Adult zebrafish were sacrificed after 24h of treatment and remove the liver， Ultrasonic homogenization treatment of zebrafish larval and collect the tissue fluid to detect the ALT， AST and LDH. HE staining was used to observe the change of liver. Meanswhile qPCR was used to detect the mRNA expressions of SREBP-1c，FAS，ACC1 and MTP， At last， Western Blot assay was used to detect the protein expression of SREBP-1c，FAS，ACC1 and MTP. RESULTS The result shows that compared with the control group， the treatmeat groups lead zebrafish larval to death obviously. And the LD₅₀ decreased with the increase of the concentration of the extractive， besides， the toxicity of ethanol extract was greater than water extract at the same concentration. The liver had a degree of hepatic steatosis in treatment groups， and the level of ALT， AST and LDH of tissue fluid in treatments were higher than control group. qPCR results showed that the mRNA of SREBP-1c，FAS and ACC1 level were significantly increased while the level of MTP level was decreased after treatmeat， Western Blot results were the same with qPCR. CONCLUSION The experiment shows that at the concentration of 40μg/mL and 80μg/mL ethanol extract of Psoralen and at the concentration of 300μg/mL and 600μg/mL water extract for 48hours will make zebrafish liver bad even to death. And the possible mechanism is related to hepatic steatosis.