Purpose: This study was designed to evaluate the resistin levels in gingival crevicular fluid (GCF) of patients suffering from periodontitis and type II diabetes mellitus (TIIDM) after non-surgical periodontal therapy and Azithromycin (AZM) as adjunctive therapy. Subjects and Methods: 48 patients with periodontitis their age ranging between (20-50) years old were selected for this study were divided into three groups: (group I): healthy patients with periodontitis, (group II): controlled TIIDM patients with periodontitis, and (group III): controlled TIIDM patients with periodontitis who were received AZM. All patients received non-surgical periodontal therapy (NSPT) and were examined with the following clinical periodontal parameters which are plaque index (PI), gingival index (GI), probing depth (PD) and clinical attachment level (CAL) at baseline, 1 month and 3 months. Collection of GCF samples was done in all patients at baseline, 4 weeks and 6 weeks. Following the periodontal therapy. Quantification of resistin in human samples was measured using resistin ELISA test. Results: NSPT was found to show relative improvement in all clinical parameters as well as a decline in resistin levels. In addition, GCF levels of resistin, GI and PI showed greater reduction after non-surgical treatment in group III than group I and II with non- significant difference. Conclusion: NSPT is found to be effective in the management of periodontitis patients with and without diabetes mellitus and also GCF resistin can be a potential biomarker to detect the periodontal disease condition. Also, adjunctive use of AZM showed clinical benefit to patients with periodontitis by its role on host response modulation.