Heavy metal pollutants are widely present in a variety of environments, and several studies have shown that exposure to heavy metals is associated with the risk of atherosclerosis. However, the underlying mechanism of this association remains unclear.AIP, as a biomarker for predicting cardiovascular events, can reflect the risk of atherosclerosis and the severity of blood vessel stenosis. Therefore, to explore the relationship between single metal and combined metal exposure and plasma atherosclerosis index. The study included data from the 2015–2016 and 2017–2020 National Health and Nutrition Examination Surveys (NHANES) and assessed the mediating role of inflammation in adults. In a single metal model, a positive dose-response relationship was observed between the blood metal selenium (Se) and AIP, and a negative correlation between cadmium (Cd) and mercury (Hg) and AIP. We construct weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR).In the WQS model, AIP increased significantly with the increase of the concentration of mixed heavy metals, while in the BKMR model, the results were consistent, with statistical significance. In addition, mediated analysis showed that HS-CRP-mediated elevations of 11.83% of blood selenium-associated AIP indicated that the metal caused an inflammatory response that aggravated atherosclerosis progression.