Abstract: Zebrafish is a novel model organism for drug metabolism research because of its small size, easy feeding, low reproduction cost and high reproduction rate.This paper outlines the construction of zebrafish metabolic model, illustrating the advantages of zebrafish model with high genetic similarity to human, well-developed enzyme system, and low substrate effect; and then reviews the application of zebrafish model in the synthesis of various new psychoactive substances such as cannabinoids, fentanyl, piperazines, and synthetic cathinones.The common metabolic reactions in zebrafish, including phase I (oxidation, N-demethylation, O-deethylation, hydroxylation and N-desalkylation) and phase II (sulfation and glucuronidation) reactions, are summarized, and the differences between the metabolites of zebrafish and those of real human body fluid samples are mainly related to the types of enzymes.This paper also points out the great potential and further research trends of zebrafish model in the study of new psychoactive substances.