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Background: Resistin is a recognized marker for chronic inflammatory conditions that could be directly linked with type 2 diabetes mellitus. This study aimed to assess serum Resistin level in type 2 diabetic patients with chronic periodontitis after non-surgical periodontal therapy. Methods: Forty individuals were recruited into three groups, group I consisted of 15 diabetic patients (type-2 diabetes mellitus) with moderate to severe chronic periodontitis, and 15 non-diabetic patients with moderate to severe chronic periodontitis in group II and group III consisted of 10 nondiabetic individuals with healthy periodontium. Non-surgical periodontal therapy with supra and subgingival debridement was performed for groups I and II. Gingival index, plaque index, probing pocket depth, clinical attachment loss, serum Resistin and high sensitivity C-Reactive Protein assay were recorded for groups I and II before and after treatment, while HbA1c was recorded for group I. Results: Both groups showed statistically significant improvement in all clinical periodontal parameters from baseline to 3 months with no statistically significant difference when comparing both groups throughout the clinical study. A highly statistically significant decrease in mean serum levels of Resistin and CRP after treatment in each group. Additionally, a statistically significant decrease in mean HbA1c level in group I was observed after treatment. Conclusion: Non-surgical periodontal therapy was effective in improving clinical periodontal parameters, serum Resistin and C-reactive protein levels after 3 months for both diabetic and nondiabetic groups.