To compare the similarity of hepatotoxicity effects of water extract from Genkwa Flos in adult zebrafish and SD rats，and to explore the action mechanism of hepatotoxicity effects of Genkwa Flos.Methods:A total of 320 adult zebrafish were divided into 32 groups(10 in each group，female:male=1:1).High，medium and low dose groups and the blank control group were set up，which were exposed for 96 hours.24 SD rats were divided into 4 groups(6 in each group).The rats of high，medium，low dose group and the blank control group were administered once a day at a dose of 2.5 mL/200 g for 7 consecutive days.The adult zebrafish and rats were then sacrificed at the end of the experiment and liver tissues were collected.The liver morphology was observed through pathological tissue sections.SOD，SDH，MDA，NOX，TG，ALT，AST were used as indicators of toxicity assessment.Based on that，the expressions of apoptosis-related gene in the liver were detected by real-time quantitative PCR.Results:Pathological tissue sections showed that Genkwa Flos could cause deformation，vacuoles，and even apoptosis of the liver cells of zebrafish.At the same time，the water extract from Genkwa Flos could cause loosely arrangement，vacuoles，morphological shrinkage，unclear boundaries，irregular nucleus morphology with hemorrhage of the liver cells of rats.The activity of SOD，SDH and NADH in the liver of adult zebrafish was significantly decreased(P<0.05)，while the activity of MDA was increased(P<0.01).The result of biochemical indexes showed that the activity of SOD，SDH in the liver of rats was significantly decreased(P<0.05)，while the activity of MDA，TG was increased(P<0.01).In addition，the activity of ALT was significantly increased(P<0.05)in low dose group，and the activity of AST was increased(P<0.01)in all drug-administered group.The result of qRT-PCR showed that the expression of genes involved in mitochondrial function(mtatp6，mtco1，mtnd1，pklr)was decreased(P<0.01)in the liver of zebrafish，the mRNA expression of genes involved in oxidative stress(gstp2，nqo1，sod1)was decreased(P<0.01)，the mRNA expression of genes involved in endoplasmic reticulum stress(atf4a，ern1，hsp90b1)was increased(P<0.01)，the mRNA expression of genes involved in autophagy(beclin-1，ATG3)was decreased(P<0.01).Conclusion:The water extract of Genkwa Flos has a toxic effect on the liver of zebrafish adults and SD rats.The mechanism may be that Genkwa Flos can induce oxidative stress damage，mitochondrial dysfunction，endoplasmic reticulum stress and zebrafish liver tissue.Cell autophagy，in turn induces liver cell apoptosis.