Inhaled toxins and particles are processed by airspace macrophages which shift them to a more M1 phenotype with the production of pro-inflammatory mediators including, IL1-β, IL-6, TNF-α which promote the recruitment of polymorphonuclear leukocytes such as neutrophils and eosinophils as well as monocytes into the airspaces to clear these toxins and particulate matter from the airspaces. However, with chronic exposure, resident M1 macrophages and new MDM phagocytic and efferocytosis functions are compromised leading to chronic low-grade inflammation and eventual bacterial colonization of airspaces. This chronic airway inflammation and bacterial colonization are associated with frequent infectious exacerbation that lead to COPD disease progression. M2 macrophages are involved in inflammation resolution, tissue remodeling and repair, but this phenotype and their function are suppressed by the chronic inflammatory insult of inhaled toxins and particulate matter. Corticosteroids exposure (either inhaled or systemic) reduce pro-inflammatory cytokine production by macrophages and shift macrophage phenotype more toward M2 phenotype and function which increase tissue reparative mediators (IL-10 and TGF-β1), increase CD206 expression (to increase pathogen recognition and processing), CD163 (to reduce pathogen survival by scavenging iron ions) and up-regulating MERTK (to enhance cell efferocytosis of apoptotic cells and cell debris). This macrophage phenotype shift will promote resolution of inflammation and tissue repair, reduce bacterial colonization thereby slowing disease progression in COPD.