<p>Macrophages serve as major defenders against pathogens, playing a crucial role in the initiation and modulation of immune responses. Age-related decline in macrophage functions is attributed to a complex network of cellular senescence and immunosenescence. The onset of cellular senescence is often a consequence of sustained oxidative stress, which is worsened by immunosenescence. Green tea catechin, epigallocatechin gallate (EGCG), has emerged as a promising candidate for promoting healthy aging by reducing cellular senescence and enhancing cytoprotective responses. However, its effectiveness in preventing oxidative stress-induced senescence and dysfunction in immune cells, particularly macrophages, remains less characterized. The present study explored the anti-senescence and cytoprotective effects of EGCG in the wake of oxidative stress-induced premature senescence in RAW 264.7 macrophages. Oxidative stress was induced in cells using repeated exposure to hydrogen peroxide (H₂O₂), followed by subsequent analyses of the degree of senescence, injury-induced apoptosis, inflammatory activity, mitochondrial stability, and alterations in macrophage functions. Senescence-associated markers p16, p21, and senescence-associated β-galactosidase were significantly up-regulated in response to prolonged oxidative stress, along with a concomitant rise in apoptosis, likely driven by oxidative damage. These alterations were accompanied by diminished phagocytosis, increased mitochondrial superoxide levels, depolarization of mitochondrial membrane potential, and augmented inflammatory responses driven by enhanced activation of nuclear factor-κB. Co-treatment with EGCG significantly mitigated these detrimental effects, reversing senescence-associated alterations and restoring both redox equilibrium and macrophage functionality. This study highlights the cytoprotective potential of EGCG in maintaining macrophage functional integrity under conditions of oxidative stress-induced senescence and cellular injury.</p>