The aim of this study was to perform a histological evaluation of sonodynamic therapy (SDT) of hematoporphyrin monomethyl ether (HMME) on artificially induced periodontal disease in rats.Submerging ligatures were placed at the subgingival region of the first maxillary molar in rats. Eighty rats were randomly assigned into four groups: group 1 received no treatment; group 2 was subjected to 50 μg/mL HMME alone; group 3 was treated with low-intensity ultrasound alone (1 W/cm(2)); and group 4 was treated with 50 μg/mL HMME plus ultrasound irradiation (1 MHz, 30 minutes). Ten rats in each group were euthanized at 7 and 15 days, and periodontal tissue samples were taken for histological examination.The animals treated by SDT showed less bone loss (P0.05).Our results suggest that HMME-mediated SDT can effectively alleviate the periodontal tissue destruction in artificially induced periodontitis in rats. Hence, SDT may have good clinic potential as a noninvasive treatment of periodontal diseases.