Background:Netrin was believed to have a regulating role on the inflammatory reaction via its receptor UNC5B. Thus it takes apart in bone destructive diseases. Periodontitis represent a localized inflammatory bone destructive disease, so Netrin-1could be involved in anti-inflammatory regulation of periodontitis. However, to the best of our knowledge, few studies were available in the literature assessing the role of Netrin-1 in periodontal health and disease. Aim:The present study was designed to assesssGCF Netrin-1and its receptor UNC5B levels in health and disease of periodontal tissues and evaluate effect of using simvastatin gel 1.2% as well as chitosan based simvastatin gel 1.2% as an adjunct to SRP on their levels. Patients and methods:The study design included 10 periodontally healthy subjects in addition to 45 systemically healthy stage II periodontitis patients divided equally into three groups andtreated bySRP, SRP+simvastatingel 1.2%and SRP+chitosanbasedsimvastatingel 1.2% (positive control & two study groups respectively). At baseline periodontalparameters were recorded and GCFsampling was performed for all participants and after treatment for periodontitis patients.Netrin-1 and and its receptorUNC5B levels were assessed by enzyme-linked immunosorbent assay. Results:Periodontal indicesat baseline inperiodontitis groupsshowed significant improvement after treatment comparedto its values at baseline. In both study groups, all periodontal parameters were significantly higher versus positive control group. At baseline, GCF levels of netrin-1 and its receptor UNC5B were significantly lower in periodontitis patients versus healthy controlsbaselineandincreasedsignificantly after receiving different treatment modalities. Conclusion:Localsimvastatingel 1.2%orchitosan basedsimvastatingel 1.2% asadjunct with SRPis effective in management of stage IIperiodontitis. Netrin-1 promotes inflammation resolution in periodontitis.