Environmental particles, such as PM2.5, diesel exhaust particles, and metal nanoparticles, are known to affect the respiratory and immune systems. Although environmental particles exhibit toxicity owing to their unique physical and chemical properties, little is known about the relationship between the bio-distribution and dynamics of environmental particles and health effects. This review introduces a novel method in which Raman microscopy is combined with histological staining, such as hematoxylin–eosin staining, immunostaining, and Diff-Quik staining, to evaluate the bio-distribution of environmental particles and the biological responses. This hybrid approach enables the visualization of environmental particles and cellular structures in the same field-of-view. Using this integrated method, we successfully visualized diesel exhaust particles and their components in respiratory epithelial cells as well as titanium dioxide particles in alveolar macrophages of mouse lung tissue and the bronchoalveolar lavage fluid. These findings demonstrate the potential of Raman microscopy for elucidating the mechanisms by which environmental particles affect the respiratory and immune systems, offering new perspectives for the management of environmental particles.