Alveolar bone loss, which is mediated by the host immune response against biofilm accumulation, is one of the most important hallmarks of periodontitis. Therefore, the current emergence of osteoimmunology has increased the interest in defining the mechanisms that underlie bone resorption in periodontal diseases. Bone remodeling is coordinated by the interaction among RANK, RANKL and OPG. OPG is a soluble decoy receptor against RANKL that inhibits its interaction with RANK, thus preventing osteoclastogenesis. It is a key factor in the inhibition of osteoclast differentiation and activation. The regulation of OPG synthesis and RANKL expression causes the activation or inactivation of osteoclasts, which profoundly affects bone remodeling The backbone of periodontal treatment consists of mechanical removal of bacterial deposits and calculus from the subgingival environment along with a strict regimen of plaque control. Incidence of disease progression is greater in sites with deeper PPD. These sites tend to respond more favorably when surgical therapy is provided. The present study was mainly carried out to identify the level of OPG in GCF, saliva and periodontal tissues of healthy and severe chronic periodontitis patients before and after MWF procedure. The study was conducted on 30 individuals, 20 of them who were suffering from severe chronic periodontitis (group A) which were subjected to treatment by MWF and (10) taken as control (group B( Preoperatively the patients received oral hygiene instructions included full mouth supra and subgingival debridement and mouth washes. After a period of 4 weeks from initial therapy, the patients were recalled. Patients with residual pockets ≥ 5mm and CAL ≥ 5mm received MWF as treatment modality. Clinical parameters were measured at day of surgery (baseline) then after 3 & 6 months postoperatively. Also GCF, saliva samples and tissue biopsies were collected at baseline then after 3 & 6 months. Supragingival scaling was repeated at the recall sessions and the patients were reinforced in oral hygiene measures. The present study observed that MWF as treatment modality cause significant improvement in all clinical parameters after 6 months. Also found significant increase in OPG level in GCF and saliva after 6 months compared to baseline. Concerning tissue biopsies, significant increase in expression of OPG was evident 6 months postoperatively in comparison to baseline. Moreover, the current study showed that there was a statistically significant inverse (negative) correlation between OPG level and PPD at baseline, also at 6 months there was a statistically significant inverse correlation between salivary OPG level and PI. However, neither GCF nor tissue showed significant correlations with different clinical variables throughout the study period. OPG is one of the important inhibitors of bone resorption in periodontal diseases. It has been shown that the rates of OPG in GCF, saliva and tissues in patients with chronic periodontitis increased proportionally with treatment. Thus, the examination of OPG may enhance the understanding of bone loss mechanism in chronic periodontitis and monitoring treatment