To analyze and identify the components of Zhibai Dihuang Pills that enter the blood and brain.Methods:Sprague Dawley(SD) rats were randomly divided into two groups，receiving either Zhibai Dihuang Pills water-honeyed solution 1.08 g/(kg·d) or saline by oral gavage for 7 days.Plasma and cerebrospinal fluid(CSF) samples were collected from both groups.Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used for analysis，employing an ACQUITYTM UPLC BEH-C18 column(2.1 mm×100 mm，1.7 μm)，with a mobile phase consisting of 0.1% formic acid aqueous solution(A) and 0.1% formic acid acetonitrile solution(B)，following a gradient elution program over 18 min at a column temperature of 40 ℃.A 2 μL injection was used in both positive and negative ion modes.The components of Zhibai Dihuang Pills that entered the blood and brain were identified by comparing the retention time，molecular weights，and secondary mass spectrometry fragments to those in a self-constructed database and relevant literature.Results:Using literature data and high-resolution secondary mass spectrometry fragment ions，68 components were identified in the serum of the Zhibai Dihuang Pills-treated rats，and 34 components were identified in the CSF，including organic acids，triterpenes，saponins，cyclic ether terpenoids，flavonoids，and phenylpropanoids.Conclusion:This study provides a preliminary exploration of the components of Zhibai Dihuang Pills that enter the blood and brain，laying the foundation for further research on the pharmacodynamic substances of this formulation.