OBJECTIVE: To study the serum pharmacochemistry of Huafengdan, and to investigate its active component base preliminarily. METHODS: UPLC-Q-TOF/MS was used to establish the fingerprints of Huafengdan and drug-containing serum of rats after intragastric administration of extract of Huafengdan (6 g/kg), Yaomu (1.37 g/kg) and Yaomu negative sample (5.73 g/kg). The fingerprints of Huafengdan and drug-containing serum were compared under positive and negative ion model, in order to preliminarily indentify the components absorbed into blood and metabolites of Huafengdan. RESULTS: Under negative ion model, 8 drug-induced constituents (3 prototype components, 5 possible metabolites) were found in drug-containing serum, 6 of which were from Yaomu. Under positive ion model, 9 drug-induced constituents (2 prototype components, 7 possible metabolites) were found in drug-containing serum, 6 of which were from Yaomu. CONCLUSIONS: The components absorbed into blood of Huafengdan are confirmed preliminarily and mainly come from Yaomu.