Ambient particulate matter (PM) exposure has been associated with atherosclerosis. However, research on the effect of real-world exposure to ambient PM in regulating visfatin expression in an animal model is very limited. The objective is to investigate whether Beijing ambient PM exposure could accelerate atherosclerosis in ApoE knockout (ApoE(-/-)) mice by upregulating visfatin expression. Forty male ApoE(-/-) mice were exposed to untreated ambient air (PM group, n = 20) or filtered air (FA group, n = 20), 24 h/day, 7 days/week, for 2 months. During the exposure, the mass concentrations of PM2.5 and PM10 in the two groups were continuously monitored. Moreover, a receptor source apportionment model was applied to apportion sources of PM2.5. At the end of the exposure, visfatin in plasma and aorta, biomarkers of inflammation, oxidative stress and lipid metabolism in blood samples, and bronchoalveolar lavage fluid (BALF) were determined, and the plaque area of the atherosclerosis lesions was quantified. PM-exposed mice were significantly higher than FA-exposed mice in terms of plasma visfatin, OxLDL, MDA, serum TC, LDL, TNF-α as well as IL-6, TNF-α, OxLDL, and MDA in BALF, while SOD and GSH-Px activities in plasma and BALF were reduced in PM-exposed mice. Pathological analysis of the aorta demonstrated that the plaque area and visfatin protein in the PM group increased significantly compared to the FA group. Our findings indicate that ambient PM exposure could accelerate atherosclerosis, which is related to visfatin upregulation, as well as the activation of inflammation and oxidative stress.