Abstract: OBJECTIVE To establish a zebrafish model of drug early evaluation, using ascorbic acid and all-trans retinoic acid as tools, so as to provide a test method for early screening of drug toxicity. METHODS The zebrafish embryos were incubated for 5 days with water as the blank control, dimethyl sulfoxide as solvent, ascorbic acid(AA) as negative drug, all-trans retinoic acid(ATRA) as positive drug. Detected the mortality, movement, organs and skeleton morphogenesis of fertilized eggs and juveniles. RESULTS 0.5% DMSO and 10 mg·L^-1 AA had weak lethal effect on zebrafish, and no obvious developmental toxicity, which could be used as cosolvent and quality control drug, respectively. ATRA had a strengthened teratogenic effect with the concentration increased, and showed a full-effect spectrum as follows:normal, slow and losed spontaneous activities, slight to severe tissues and organs malformations, vertebra mineralization inhibition. It provided a good reference for the evaluation of drug toxicity, and ATRA 7.5 μg·L^-1 could be selected as the positive control drug evaluated concentration. CONCLUSION The zebrafish model designed with AA and ATRA reasonably can be used for early evaluation of drug toxicity.