Abstract: The whole dried plant of Erigeron breviscapus is clinically used in traditional Chinese medicine, and named as “Deng-Zhan-Xi-Xin”. The herb is primarily distributed in Yunnan, Guangxi, and Guizhou provinces of China, and its traditional therapeutic effects include promoting blood circulation, unblocking meridians, relieving pain, dispelling wind and cold. Nowadays, it is commonly prescribed for pathological conditions including hemiplegia, coronary heart disease, cerebral thrombosis, rheumatism, and microcirculatory disorders. Pharmacological studies have demonstrated its neuroprotective effects, such as microcirculation improvement, lipid-lowering activity, and inhibition of platelet aggregation. Chemical components including caffeoyl acid and its analogues, as well as flavonoids and their glycosides, have been reported, and the flavonoid glycoside of scutellarin has regarded as an active component related to the efficacy of the herb. Current in vivo pharmacokinetic studies on E. breviscapus have mostly focused on its injectable formulations or pure compounds in normal rats, while multi-component pharmacokinetic studies of its aqueous decoction in vascular dementia (VaD) rat models remain insufficient. As a result, the study established a bilateral common carotid artery occlusion-induced VaD rat model, which better represented clinical cases. The pharmacokinetics of multiple blood-absorbed components from the aqueous decoction was investigated by ultra-high performance liquid chromatography coupled with quadrupole-linear ion trap mass spectrometry (UHPLC-Qtrap-MS/MS). Furthermore, network pharmacology analysis was employed to predict the potential targets of these components, and interaction networking for compound-protein-pathway was constructed. The UHPLC-Qtrap-MS/MS technique was employed to quantitatively analyze the content changes of six components, including apigenin, scutellarin, syringic acid, salicylic acid, apigenin-7-O-glucuronide and scopoletin in the plasma of rat model of vascular dementia. Additionally, the pharmacokinetic parameters were calculated. A gradient elution was performed on an ACQUITY UPLC HSS T3 chromatographic column (100 mm×2.1 mm, 1.8 μm), using 0.05% formic acid-water as mobile phase A and acetonitrile as mobile phase B. A quantitative analytical method was established by optimizing declustering potential (DP) and collision energy (CE) values, followed by comprehensive methodological validation covering specificity, linearity, precision, accuracy, stability, extraction recovery, and matrix effects. Mass spectrometry detection was conducted under multi-reaction monitoring (MRM) mode with electrospray ionization source (ESI). Subsequently, the DAS 2.0 software was utilized to calculate detailed pharmacokinetic parameters. The network pharmacology method was applied to construct a network of chemical components-disease targets-metabolic pathways. Based on the blood-absorbed components, the potential active targets were inferred. The analysis results showed that, compared with the sham-operated group, the in vivo exposure of syringic acid, scutellarin, scopoletin, and salicylic acid in the vascular dementia model group is lower, which may be attributed to accelerated metabolism and increased excretion of these components. Additionally, scutellarin, salicylic acid, and apigenin-7-O-glucuronide exhibites a double-peak absorption, suggesting a possible enterohepatic circulation phenomenon. Among all detected active components, scutellarin has the highest in vivo exposure. Network pharmacology analysis revealed that the components act on a total of 12 disease targets and are related to 5 signaling pathways. The active ingredient scutellarin mainly exertes a therapeutic effect on vascular dementia by acting on the mitogen-activated protein kinase (MAPK) signaling pathway. The potential multi-target mechanisms of E. breviscapus via network pharmacology remains experimental validation in future. These rational findings provide support for the pharmacokinetic study of E. breviscapus and offer a reference for deeper understanding of its mechanism of action.