Particulate matter ≤ 2.5 µm (PM2.5) poses health risks related to various diseases and infections. However, the interactions between PM2.5 and cells such as uptake and cell responses have not been fully investigated despite advances in bioimaging techniques, because the heterogeneous morphology and composition of PM2.5 make it challenging to employ labeling techniques, such as fluorescence. In this work, we visualized the interaction between PM2.5 and cells using optical diffraction tomography (ODT), which provides quantitative phase images by refractive index distribution. Through ODT analysis, the interactions of PM2.5 with macrophages and epithelial cells, such as intracellular dynamics, uptake, and cellular behavior, were successfully visualized without labeling techniques. ODT analysis clearly shows the behavior of phagocytic macrophages and nonphagocytic epithelial cells for PM2.5. Moreover, ODT analysis could quantitatively compare the accumulation of PM2.5 inside the cells. PM2.5 uptake by macrophages increased substantially over time, but uptake by epithelial cells increased only marginally. Our findings indicate that ODT analysis is a promising alternative approach to visually and quantitatively understanding the interaction of PM2.5 with cells. Therefore, we expect ODT analysis to be employed to investigate the interactions of materials and cells that are difficult to label.