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AP was induced by pulp exposure of mandibular first molars and allowed to develop for 28\u2009days. Animals in caffeine groups received 10\u2009mg\/kg\/day by orogastric gavage during the experimental period. The antioxidant capacity of caffeine was assessed by DPPH\u2022 and ABTS\u2022\u2009+\u2009assays. Systemic oxidative status was evaluated by blood reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). Histology, Picro\u2010Sirius red staining for collagen, and micro\u2010computed tomography (micro\u2010CT) analysis of alveolar bone (BV\/TV, Tb.N, Tb.Sp, porosity, lesion volume) were performed. Molecular docking against adenosine A\n                      <jats:sub>1<\/jats:sub>\n                      and A\n                      <jats:sub>2<\/jats:sub>\n                      <jats:sub>A<\/jats:sub>\n                      receptors was used to probe caffeine\u2013receptor interactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Caffeine showed relevant radical\u2010scavenging activity in\u00a0vitro (DPPH\u2022 assay). AP induced systemic redox imbalance, marked inflammatory infiltration, collagen loss and increased lesion volume. Moderate caffeine intake restored redox markers (\u2191GSH, \u2193TBARS), attenuated inflammatory infiltrate, preserved collagen content and reduced lesion volume (AP\u2009+\u2009caffeine vs. AP;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Micro\u2010CT demonstrated improved alveolar bone microarchitecture in AP\u2009+\u2009caffeine group (increased BV\/TV and Tb.N; reduced Tb.Sp and porosity). Molecular docking indicated stable hydrophobic and hydrogen\u2010bond interactions of caffeine within A\n                      <jats:sub>1<\/jats:sub>\n                      and A\n                      <jats:sub>2<\/jats:sub>\n                      <jats:sub>A<\/jats:sub>\n                      receptor binding pockets, supporting an antagonistic effect on adenosine signalling consistent with reduced pro\u2010inflammatory activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Moderate systemic caffeine (10\u2009mg\/kg\/day) attenuates apical periodontitis progression and preserves alveolar bone quality in rats, associated with antioxidant activity and a probable modulation of adenosine receptor\u2010mediated inflammatory pathways.<\/jats:p>\n                  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