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AIM To evaluate the effect of excessive caffeine intake on the inflammation/resorption processes associated with periapical periodontitis (PP) in rats. METHODOLOGY Sixteen Wistar rats were used. Periapical periodontitis was induced in the four first molars in each animal. The animals were arranged into two groups: control (C) - rats with periapical periodontitis; and caffeine (CAF) - rats with periapical periodontitis under caffeine administration protocol. The CAF animals received 10 mg/100 g of body weight/day of caffeine via gavage starting fifteen days before PP induction and continuing for thirty more days until euthanasia. On the 30th day the animals were euthanised, and the jaws removed for micro-computed tomography, histological, and immunohistochemical analysis for RANKL, OPG, TRAP, IL-10, TNF-⍺ and IL-1β. The Mann-Whitney test was performed for nonparametric data, and Student t-test test was performed for parametric data, using p<0.05. RESULTS There was no significant difference in the weight change between the groups. The median score of the inflammatory process was significantly greater in the CAF group (3) compared to the C group (2), p = 0.0256. Bone resorption was greater in the group consuming caffeine (1.08 mm3 ± 0.15 mm3 ) compared to the C group (0.88 mm3 ± 0.10 mm3 ), p = 0.0346. The immunolabelling for RANKL, TRAP, and IL-1β was significantly higher in the CAF group when compared to the control, p < 0.05. No differences were found for the OPG, IL-10, and TNF-⍺ immunolabeling. CONCLUSION Excessive caffeine exposure via gavage in rats was able to exacerbate the volume of periapical bone destruction, and the inflammatory pattern deriving from periapical periodontitis altering the expression of RANKL, IL-1β, and TRAP.