Background. Periodontitis is a progressive lesion of periodontal tissues and one of the most important causes of tooth loss. According to recent publications, periodontitis affects from 11% to 50% of the world’s adult population. Therefore, the problem of developing effective methods for treating and preventing this disease remains relevant. Metabolic disorders in the periodontium are known to contribute to the development of periodontitis. A pronounced change in hemodynamics and microcirculation leads to trophic disturbance of periodontal tissues, thus triggering the development of pronounced hypoxia in these tissues. Thus, prevention and elimination of hypoxia is one of the most important stages of pathogenetic treatment. Objective. To experimentally evaluate the efficacy of injectable carboxytherapy in the treatment of periodontal diseases using an in vivo model of periodontitis in rats. Methods. A preclinical experimental study was conducted on 30 sexually mature Wistar rats. The animals were randomly divided into 4 groups, including I–III experimental groups (n = 27) and a control group (n = 3). In all experimental groups, periodontitis was modelled. In group I (n = 9), no treatment was performed. In group II (n = 9), carboxytherapy with a carbon dioxide flow rate of 5 ml/min was conducted. In group III (n = 9), carboxytherapy with a flow rate of 10 ml/ min was conducted. The experimental animals were injected with carbon dioxide once, twice, or three times 7 days after surgical intervention at weekly intervals. The efficacy of injected carboxytherapy in rat periodontium with respect to the control was evaluated by histologic analysis. The norm criteria were the lamellar structure of compact alveolar bone, the presence of periodontal ligament between the alveolar bone and the tooth, represented by oriented collagen fibers with orderly arranged fibroblasts between them (final signs). The intermediate outcome was considered based on the launch of neovascularization and neocollagenogenesis processes. The criterion of neovascularization and neocollagenogenesis activation was considered to be an increase in the number of young collagen fibers, an increase in fibroblast-like cells of outgrowth form with a high expression of procollagen in the connective tissue matrix (intermediate signs). Integral indices on intermediate signs and on final signs were brought to normalized indices as a fraction of the maximum possible sum of points in the group. The dynamics of the normalized indicator for intermediate and final signs was considered. The results were processed using IBM SPSS Statistics version 26 (IBM Inc., USA). Results. The histological study of the mandible of rats from group I demonstrated that the destruction of the periodontal ligament in the absence of treatment leads to the widening of the periodontal gap, accompanied by inflammatory processes and thinning of collagen fibers due to the growth of edema, the appearance of resorption lacunae and, further, to the resorption of alveolar bone. At the same time, groups II and III showed a gradual decrease in the inflammatory reaction, formation of young collagen fibers, and, as a consequence, restoration of the periodontal space. In these groups, the histologic pattern corresponded to the norm in the case of three times carboxytherapy injection with a flow rate of 5 ml/min and already in the case of two times injection with a flow rate of 10 ml/min. Conclusion. The use of injectable carboxytherapy to treat periodontal ligament lesions not only restores its microarchitectonics, but also prevents further resorption of alveolar bone. This may have a positive effect in the treatment of periodontal disease.