Abstract Background Recently, the impact of PM2.5 on human health has been intensively studied, especially the respiratory system. High-density lipoprotein plays a crucial role in removing excess cholesterol from cells and transporting it to the liver for excretion. However, the effects of ambient PM2.5 on high-density lipoprotein (HDL) level have not been further studied. Our research aims to investigate the potential association between ambient PM2.5 concentrations and high-density lipoprotein (HDL) levels within the middle-aged and older adults in China. Methods We employed data from individuals aged 45 years and above who were participants in Wave 3 of the China Health and Retirement Longitudinal Study (CHARLS). The high-quality, high-resolution PM2.5 exposure concentration data for each participant were obtained from the ChinaHighAirPollutants (CHAP) dataset, while the HDL levels were derived from blood samples collected during CHARLS Wave 3. This analysis constitutes a cross-sectional study involving a total of 12,519 participants. To investigate associations, we conducted multivariate linear regression analysis, supplemented by subgroup analysis. Results In this cross-sectional investigation, we discerned a negative association between prolonged exposure to ambient PM2.5 constituents and high-density lipoprotein (HDL) levels. The observed correlation between ambient PM2.5 and HDL levels suggests that older individuals residing in areas with elevated PM2.5 concentrations exhibit a reduction in HDL levels (Beta: -0.045; 95% CI: -0.056, -0.035; P