Abstract: To obtain chemical constituent information of rat plasma after oral administration of Huang-Lian-Jie-Du Decoction (HLJDD), a LC-FT-ICR-MS method has been established, and both positive and negative ions scan modes were include in the analysis. By comparing their retention time, high resolution mass data of HLJDD extracts, blank plasma and dosed plasma, 38 constituents, including 22 prototype compounds and 16 metabolites, were detected in rat plasma after oral administration of HLJDD. In the 22 prototype compounds, 16 constituents were determined unambiguously by comparing with references. In the analysis of metabolites, phase Ⅱ reactions like glucuronidation and sulfation were the major biotransformation pathways of HLJDD. M11 was observed as the only phase I metabolite in present experiment. The results will be beneficial for the further pharmacokinetics and pharmacological evaluations of HLJDD.