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Inflamm-aging was recently affiliated with the progression of diabetic complications. Local cellular senescence together with senescence-associated secretory phenotype (SASP) are the main contributors to inflamm-aging. However, little is known about their involvement in diabetic periodontitis. Gingiva is the first line of host defense in the periodontium, and macrophages are key SASP-carrying cells. Here, we explored the molecular mechanism by which hyperglycemia drives the inflamm-aging in the gingival tissue of diabetic mice and macrophages. We demonstrated that hyperglycemia increased the infiltrated macrophage senescence in gingival tissue of diabetic mice. Simultaneously, hyperglycemia elevated the local burden of senescent cells in gingival tissue and induced the serum secretion of SASP factors in vivo. Moreover, in vitro, high glucose induced macrophage senescence and SASP factors secretion …