This study aimed to investigate the effect of pomegranate extract (PE) on the progression of periodontal disease in an experimental rat model of periodontitis. Periodontitis was induced in rats by placing a 5-0 black silk ligature and injecting a lipopolysaccharide of Porphyromonas gingivalis into the gingiva. Distilled water (DW) or PE solution was orally administered daily, and the animals were sacrificed after 3 weeks. Tissue specimens of the periodontitis model were analyzed using an enzyme-linked immunosorbent assay kit and by micro-computed tomography (CT) imaging. The expression levels of cyclo-oxygenase (COX)-1 and COX-2 were significantly reduced in ligation (Lig)+PE 22 µg/mL and Lig+PE 44 µg/mL groups, but there was no statistically significant difference in matrix metalloproteinase (MMP)-8 levels. Furthermore, micro-CT imaging demonstrated that alveolar bone resorption was inhibited in Lig+PE 22 µg/mL and Lig+PE 44 µg/mL groups compared with that in the Lig+DW group. These results demonstrate that PE has an inhibitory effect on the progression of alveolar bone loss caused by periodontal inflammation by reducing the expression levels of COX-1 and COX-2 in the process of periodontal disease.