Objective: To evaluate the therapeutic effect of local injection of stem cells from human exfoliated primary teeth (SHED) on periodontitis in mice. Methods: Fifteen female mice were randomly divided into three groups: normal control group, periodontitis group and SHED treatment group. A periodontitis model was established by ligating a 0.2 mm orthodontic ligation wire to the maxillary first molar. The SHED group was injected with SHED at 3 weeks post-ligation. All mice were sacrificed and their maxillae were dissected five weeks post-ligation. Clinical assessments, micro-computed tomography (micro-CT) scanning, and histologic examination were used to evaluate the outcome of tissue regeneration. Results: Micro-CT analysis showed that SHED administration significantly increased periodontal regeneration and decreased the distance between the cemento-enamel junction and the alveolar bone crest. In addition, histopathological photomicrographs showed new regenerated bone, the number of TNF-α-positive, IFN-γ-positive and CD4+ cells decreased, and osteoclasts-positive decreased in the periodontal defect area in the SHED group compared with the periodontitis group. Conclusion: SHED administration suppresses the expression of inflammatory factors, inhibits the production of osteoclasts, and promotes the regeneration of periodontal tissues. Schlagwörter: periodontitis, stem cells from primary teeth, inflammation