INTRODUCTION: This study evaluated the impact of dealcoholized red wine polyphenols on the inflammation and lesion volume associated with apical periodontitis (AP) in rats. METHODS: Thirty-two Wistar rats receiving AP induction were arranged as: Control Group (C), Dealcoholized Red Wine Group (DRW), Red Wine Group (W), and Alcohol Group (ALC). Solutions were administered daily in a volume of 4.28 mL/kg via gavage for 45 days. Mandibles and maxillae were removed for histological, immunohistochemical (IL-1β, IL-10, TNF-α, RANKL, OPG, TRAP) and micro-computed tomography analyses of the AP site. A statistical analysis was performed with a significance level of 5%. RESULTS: Inflammation and TRAP-positive cell count were similar for DRW and W, but lower when compared to C and ALC (p<
0.001). The immunohistochemical expression of OPG was higher for DRW than for ALC (p<
0.05). A larger lesion volume was observed in ALC compared to other groups (p<
0.001). CONCLUSIONS: Prophylactic administration of dealcoholized red wine significantly reduced inflammation, decreased the number of TRAP-positive cells, enhanced OPG expression, and reduced lesion volume compared to water and alcohol solutions.