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BACKGROUND Mensenchymal stem cell therapy brings hope for regenerating damaged periodontal tissues. OBJECTIVE The present study aimed to investigate the therapeutic role of local BMSCs injection in ligation-induced periodontitis and the underlying mechanisms. METHODS Alveolar bone lesion was induced by placing ligatures subgingivally around the bilateral maxillary second molars for 28 days. The alveolar bone lesion was confirmed by micro-CT analysis and bone histomorphometry. Allogeneic bone marrow stem cells (BMSCs) transplantation was carried out at 28 day after ligation. The survival state of the transplanted BMSCs was observed by bioluminescent imaging. The implantation of the BMSCs into the gingival tissues and periodontal ligament was confirmed by green fluorescent protein (GFP) immunohistochemical staining. The expression level of pro-inflammatory, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) in periodontal tissues were evaluated by immunohistochemical staining and realtime-PCR. RESULTS Significant reverse of alveolar bone lesion was observed after BMSCs transplantation. The expression of TNF-α and IL-1β was down-regulated by BMSCs transplantation. The number of tartrate resistant acid phosphatase (TRAP)-positive osteoclasts in the periodontal ligament was reduced, and the increased RANKL and decreased OPG expression was also reversed after BMSCs transplantation. CONCLUSION It is concluded that allogeneic BMSCs local injection could inhibit the inflammation of the periodontitis tissue and promote periodontal tissue regeneration. This article is protected by copyright. All rights reserved.