Particulate matter 2.5 (PM2.5) promotes the accumulation of Ca2+ in the cytoplasm of macrophages by activating endoplasmic reticulum stress in macrophages, which in turn affects the study of atherosclerotic plaques in ApoE-/-mice. Methods In vivo experiments Twenty-four 8-week-old ApoE-/-mice were randomly divided into control group (n=12) and PM2.5 group (n=12) and fed with high-fat diet for 8 weeks, in which the control group was given normal saline by tracheal instillation and the PM2.5 group was given PM2.5 normal saline suspension by tracheal instillation (30 mg/kg/d). After 8 weeks, paraffin sections of aortic roots were stained with movat, and the levels of oxygen free radicals (ROS) were detected by DHE. The apoptosis of cells in plaques was detected by TUNEL. The expression of inflammatory factors IL-6, TNF-α and MCP-1 downstream of endoplasmic reticulum stress was detected by Western Blot. After isolation and culture of mouse primary peritoneal macrophages in vitro, the cells were divided into: 1. Control group: no stimulation, 2. Model group: LPS 100ng/mL (24h), 3. LPS+PM2.5 (24h). Results In vivo experiments showed that the area of atherosclerotic plaque was significantly increased and ROS level was significantly increased in PM2.5 group (P＜0.001). The number of necrotic and apoptotic cells in the plaque was significantly increased, and the expression of inflammatory factors IL-6, TNF-α, MCP-1 protein downstream of endoplasmic reticulum stress was increased (P＜0.001). In vitro experiment, compared with LPS group, the accumulation of intracellular Ca2+ was significantly increased in LPS+ PM2.5 group (P＜0.001), and the expression of IL-6, TNF-α, MCP-1 protein was increased (P＜0.001). Conclusion In PM2.5-treated ApoE /-mice fed with high-fat diet, PM2.5 can act on macrophages and activate their endoplasmic reticulum stress, leading to increased accumulation of Ca2+ in the cytoplasm of macrophages, increasing the production of oxygen free radicals and the number of cell necrosis and apoptosis in plaques, thus promoting the progression of atherosclerotic plaques