Jiao-Tai-Wan, which is composed of Coptis Rhizoma and Cinnamon Cortex, has been recently used to treat type 2 diabetes. Owing to lack of data on its prototypes and metabolites, elucidation of the pharmacological and clinically safe levels of this formula has been significantly hindered. To screen more potential bioactive components of Jiao-Tai-Wan, we identified its multiple prototypes and metabolites in the plasma of type 2 diabetic rats by ultra high performance liquid chromatography/quadrupole-time-of-flight mass spectrometry. A total of 47 compounds were identified in the plasma of type 2 diabetic rats, including 22 prototypes and 25 metabolites, with alkaloids constituting the majority of the absorbed prototype components. In addition, this is the first study to detect vanillic acid, gallic acid, chlorogenic acid, protocatechuic acid, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid, 4-hydroxycinnamic acid, and 2-methoxy cinnamic acid after oral administration of Jiao-Tai-Wan. The prototypes from Jiao-Tai-Wan were extensively metabolized by demethylation, hydroxylation, and reduction in phase â ?metabolic reactions and by methylation or conjugation of glucuronide or sulfate in phase â ?reactions. This is the first systematic study on the components and metabolic profiles of Jiao-Tai-Wan in vivo. This study provides a useful chemical basis for further pharmacological research and clinical application of Jiao-Tai-Wan. CI - (c) 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.