The purpose of this study was to evaluate the effects of administered Paeoniflorin (Pae) on periodontal tissues within an experimental periodontitis model. Forty male Wistar rats were used in this study and experimental periodontitis was created in all rats except in the control group (n = 10, first group). In the periodontitis group, experimental periodontitis was created but no other application was performed (n = 10, second group). In the other groups created experimental periodontitis, systemic Pae (n = 10, third group) or saline (n = 10, fourth group) was applied. A biochemical analysis of the gingival vascular endothelial growth factor (VEGF) levels and a histomorphometric analysis (measurements of the area of alveolar bone, alveolar bone resorption, and attachment loss) were performed. In the Pae group, the area of the alveolar bone was increased, while alveolar bone resorption and attachment loss decreased. Gingival VEGF levels increased in all groups that created experimental periodontitis and the greatest increase seen in the Pae group. Histomorphometric and biochemical analyses in this study suggest that Pae has a curative effect on periodontal tissues. However, additional studies are needed to confirm these results.