Particulate matter (PM) imposes a significant impact to environmental health with deleterious effects on the human pulmonary and cardiovascular systems. Macrophages (Mφ), key immune cells in lung tissues, have a prominent role in responding to inhaled cells, accommodating inflammation, and influencing tissue repair processes. Elucidating the critical cellular responses of Mφ to PM exposure is essential to understand the mechanisms underlying PM-induced health effects. The present review aims to give a glimpse on literature about the PM interaction with Mφ, triggering the cellular events causing the inflammation, oxidative stress (OS) and tissue damage. The present paper reviews the different pathways involved in Mφ activation upon PM exposure, including phagocytosis, intracellular signaling cascades, and the release of pro-inflammatory mediators. Potential therapeutic strategies targeting Mφ-mediated responses to reduce PM-induced health effects are also discussed. Overall, unraveling the complex interplay between PM and Mφ sheds light on new avenues for environmental health research and promises to develop targeted interventions to reduce the burden of PM-related diseases on global health.