Purpose: to evaluate the effect of PRF system (PRF mixed with bone graft) in the regeneration of intra-bony defects by assessing osteocalcin in gingival Crevicular fluid. This study was accomplished on periodontal clinical and Radiographic evaluation.Subjects and Methods: A randomized double blind, split-mouth study was undergone on 12 patients with twenty four intrabony defects the selected defects were randomly divided into Group I (Test group): including eight defects that received PRF mixed with grafting material. Group II (Collagen group): including eight defects that received collagen membrane and PRF mixed with grafting material and Group III (Control group): including eight defects that received open flap debridement only. All subjects were put on a recall schedule where the clinical parameters (PI, GI, PD and CAL) and radiographic assessment(Alveolar bone height and bone density) were measured and recorded at base line and six months postoperatively. Results: Clinical outcomes in defects treated with collagen membrane and PRF mixed with grafting material (group II) showed more pocket reduction, greater gain in attachment level compared to other groups. However, better improvement in radiographic parameters was observed in defects treated with PRF mixed with grafting material (group I). Regarding mean osteocalcin concentration, defects treated with collagen membrane and PRF mixed with grafting material (group II) reported maximum reduction at the end of the study. Conclusions: The use of PRF as a regenerative material in managing periodontal intrabony defects resulted in pocket depth reduction, clinical attachment gain and defect fill with comparable results to bone graft and collagen membrane.