Introduction: Intermittent administration of parathy raid hormone (PTH) promotes oral osseous wound healing and protects against ligature-induced alveolar bone loss. However, its therapeutic value on periapical periodontitis is unknown. The goal of this study was to determine the effect of intermittent PTH administration on the progression of periapical periodontitis. Methods: Seven lymphotoxin alpha deficient mice received pulp exposures of mandibular first and second molars. Exposed pulp in the right mandible was covered with plaque-contaminated fibrin, whereas exposed pulp in the left mandible was left open. After 4 weeks, the perk apical tissues were examined to determine the effect of plaque-contaminated fibrin to induce periapical lesions. Fourteen mice received pulp exposure covered with plaque-contaminated fibrin. PTH (40 Ag/kg/d) was administered intermittently to half of the mice for 3 weeks beginning 1 week after pulp exposure. The remaining half received saline injections as the vehicle control. At sacrifice, mandibles and tibiae were harvested and processed for histologic examination. Evaluation of neutrophils and blood vessels was performed after staining with immunofluorescence, and periradicular bone was histomorphometrically analyzed. Results: The exposed pulp covered with plaque-contaminated fibrin resulted in significantly larger periapical lesions compared with the control. Intermittent PTH administration reduced the size of periapical lesions significantly. Significantly less neutrophil infiltration around the root apex was found in PTH-treated animals compared with the control. Conclusions: PTH treatment suppressed periapical inflammation by reducing neutrophil infiltration and protected against tissue destruction by periapical periodontitis.