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Introduction: Periodontal disease in its advanced chronic forms, can involve all or parts of periodontium. While periodontal diseases are accompanied with extensive destruction of periodontal tissues (include-ing cementum, alveolar bone, gingival and periodontal ligament), the tissue has a limited ability to regenerate itself. Due to the limited regenerating capacity of the tissue, application of cells with high pote-ncy of regeneration may be for the treatm-ent of periodontal disease. Materials & Methods: Cord blood was collected from the umbilical cord vein of 30 mothers who gave informed consent. The isolated mononuclear cell layer was washed in PBS, and then re-suspended in growth medium. The cells were analyzed with flowcytometry for superficial mar-kers. Critical-sized (8 mm) calvarial defe-cts were created in the parietal bone of ad-ult rabbit. Defects were either left empty, treated with a collagen alone, or a collagen with human cord blood-derived mesenc-hymal stem cells (USSCs). Histology and histomorphometry were performed. Finding: USSCs were positive for the markers CD73 and CD105, negative for the marker CD34 and had the normal kary-otype 44XX. Quality of the regenerated bone and its connection to surrounding bone tissue were significantly improved in the treated rabbits. Discussion & Conclusions: Results of the study demonstrated that from the viewpoint of histomorphometric, the rate of lesion regeneration was about 90% higher in the treatment group and the complete reconst-ruction was accomplished after 8 weeks