Abstract: Objective：To investigate the effect of hydrogel loaded with erythropoietin (EPO) on the experimental periodontal disease (EPD) in rats.Methods：Hydrogel loaded with EPO was prepared, and measured for the gelation time and the effect on the growth and adhesion of BMSCs. Wistar rats were injected with 25 μL of the solution on the proximal and distal alveolar crest of the maxillary first molar immediately after EPD induction once every 3 days for 14 days. CBCT was used to detect the distance between cemento-enamel junction between the first molar and the second molar and alveolar bone crest; HE staining was used to observe the morphological changes of the tissue sections. The degree of inflammatory cell infiltration, alveolar bone and cementum integrity between the first molar and the second molar was evaluated by 0~3 grade. Results：The gelation time of hydrogels loaded with EPO was (220±15)s and BMSCs grew well with good adhesion. The results from the CBCT analysis demonstrated that animals treated with EPO showed no significant bone resorption and alveolar bone height was significantly greater than that of the control group, close to that of the blank group. Histopathological analysis confirmed the healthy bone structure for naive group animals, while the EPD group exhibited bone loss. In particular, the EPD+hydrogel loaded with EPO group showed significantly alveolar bone regeneration, The results of these groups were significantly different from the EPD+hydrogel loaded with EPO group (P<0.05). Conclusions：Our data suggests that hydrogel loaded with EPO was able to control periodontitis and promote alveolar bone regeneration, and may provide a new therapeutic strategy for periodontitis.