Aim:This study was designed to evaluate the resistin levels in GCF of patients with periodontitis and type 2 diabetes mellitus(T2DM) after non-surgical periodontal therapy and subantimicrobial dosage doxycycline(SDD).Subjects & Methods:Thirty periodontal sites within 24 patients with age ranged between(24-51) years old were selected for this study.Total of 30 periodontal sites were randomly divided into three groups;each group included ten periodontal sites:(group I):systemically healthy periodontitis patients who were received scaling and root planning (SRP),(group II):periodontitis patients with T2DM who were received SRP, and(group III):periodontitis patients with T2DM who were received SRP and SDD 20mg twice/day. All patients were examined with clinical periodontal parameters: plaque index(PI), gingival index(GI), probing depth(PD) and clinical attachment level(CAL).Patients in each groups underwent nonsurgical periodontal therapy combined with a maintenance program (including brushing with regular toothpaste). GCF samples were collected in all patients at baseline, one month as well as 3 months after periodontal therapy. Quantification of resistin in human samples was measured using resistin ELISA test. Results: Non-surgical periodontal therapy resulted in relative improvement in all clinical parameters as well as a decrease in resistin levels.In addition, GCF levels of resistin, PD , GI were greater reduction after non-surgical treatment in group III than group II.Conclusions:Non surgical periodontal therapy is found to be effective in the treatment of periodontitis patients with and without diabetes mellitus and also GCF resistin can be a useful biomarker to detect the periodontal disease condition.Also, adjunctive use of SDD showed more clinical benefit to patients with periodontitis by host response modulation.