Background: Salvianolic acid B (SAB), tanshinone IIA (TIIA), ginsenoside Rg1 (GRg1) and ginsenoside Rb1 (GRb1) are the main active components of Danshen-Sanqi herbal pair (DS-SQ), which is widely used in the treatment of cardiovascular diseases in Asia. The compatibility mechanisms of compound Chinese herbal preparation may be clarified to some degree by understanding the interactions of the active components based on their metabolic research. Furthermore, zebrafish is a convenient and feasible model to study the metabolism of drugs. Objective: To investigate the metabolism of SAB, TIIA, GRg1 and GRb1 in zebrafish by liquid chromatographytandem mass spectrometry (LC-MS/MS) analysis. Methods: Zebrafish embryos after 48-hour hatching were divided into nine experimental groups. The blank group was exposed to 1 mL ultra-pure water. Eight drug-treated groups were exposed to 1 mL solution of SAB, TIIA,GRg1, GRb1, SAB and GRg1, SAB and GRb1, TIIA and GRg1, TIIA and GRb1, respectively. After homogenization,they were analyzed by LC-MS/MS. The Structures of the metabolites were determined by analyzing their corresponding mass spectra information and comparing the data with relevant literature. According to the change of the amount of metabolites, the metabolic effect between SAB, TIIA, GRg1 and GRb1 were investigated. Results: Eighteen metabolites and four parent drugs of SAB, TIIA, GRg1 and GRb1 in zebrafish were identified by LC-MS/MS, including methylation, degradation, reduction, dehydrogenation, hydroxylation, desugarization and glucuronidation metabolites. Furthermore, after being combined exposed of drugs, GRg1 and GRb1 could promote the metabolism of TIIA, while SAB and TIIA could promote the metabolism of GRg1 and GRb1 to different degree. Conclusion: By using LC-MS/MS analysis, zebrafish was successfully applied to study the metabolism of SAB,TIIA, GRg1 and GRb1, which is significance to explain the possible synergistic effect of components in DS-SQ through modifying the metabolism in zebrafish. This study can be helpful for the further research of DS-SQ.