Vascular inflammation is a common pathological basis underlying many cardiovascular diseases. As such, the treatment of vascular inflammation has attracted increasing attention. The Piezo1 pathway has long been shown to play an important role in the development of vascular inflammation. Jatrorrhizine (Jat) is an effective component of Rhizoma Coptidis. It is commonly used in the treatment of inflammatory diseases and is a potential drug for the treatment of vascular inflammation. However, its mechanism of action on vascular inflammation remains unclear, as is the effect of Jat on Piezo1. Therefore, we conducted a series of studies on the effect of jatrorrhizine on vascular inflammation in vivo and in vitro. In this study, the effect of Jat treatment on H2O2-induced endothelial cell inflammation was investigated in vitro, and the potential mechanism of Jat was explored. In in vivo experiments, we investigated the effect of jatrorrhizine on vascular inflammation induced by carotid artery ligation and its effect on the Piezo1 signaling pathway. We found that Jat could reduce the severity of carotid intimal hyperplasia and local vascular inflammation in mice. In the H2O2-induced inflammation model, cell proliferation and migration were significantly inhibited, and the expression of pro-inflammatory factors was reduced. Importantly, the addition of Jat to endothelial Piezo1 knockout did not produce further significant inhibition. We believe that the role of Jat in the treatment of vascular inflammation may be related to Piezo1. And we believe that Jat has great potential in the treatment of vascular inflammation and cardiovascular diseases.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.