Introduction: over the last years, in Cuba and other countries, encouraging results have been obtained in different medical specialties in the field of tissue regeneration by implanting stem cells; it has motivated us to consider periodontal tissue as a target for this therapy. Objective: To determine the efficacy of the implant of mononuclear autologous cells for the treatment of 48 months evolution chronic periodontitis. Material and Methods: 30 patients attending the Periodontology Clinic of the "Enrique Cabrera" hospital for over48 months during years 2008 to 2014 where included in the study, divided into two groups 15 patients each: group A were treated with autologous mononuclear cells and group B, who underwent classic therapy. The peripheral blood autologous mononuclear cells (MNC-SP) were mobilized with granulocyte colony- stimulating factor (G-CSF). Results: group A patients showed a significant average decrease in all clinical variables, more remarkable in every of the evolution periods as compared to the initial stage of every patient at 6, 12, 24 and 48 months after starting the treatment. In Group B patients, signs of the disease gradually reappeared as the post-treatment period proceeded. Conclusions: regenerative cell therapy with MNC-SP is effective and long lasting in patients with periodontitis.