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Purpose: A novel acute-phase protein, YKL-40, is known as an inflammation-associated glycoprotein. YKL-40 is shown to be linked to inflammation, endothelial dysfunction and tissue remodeling secreted by various cells and is also considered to be stimulated by cytokines such as interleukin-6 (IL-6). The present study aimed to investigate YKL-40 and IL-6 levels in saliva and gingival crevicular fluid (GCF) of patients with chronic periodontitis (CP) after non-surgical periodontal therapy for the first time., Materials and Methods: Twenty-six CP patients and 26 periodontally healthy individuals were enrolled. Clinical measurements were recorded; saliva and GCF samples were obtained at baseline and 1 and 3 months after non-surgical periodontal therapy. Levels of YKL-40 and IL-6 in saliva and GCF were analysed by ELISA., Results: Salivary and GCF YKL-40 and IL-6 levels were found to be statistically significantly higher in CP patients compared to healthy controls at baseline (p < 0.001). At 1 and 3 months after the completion of treatment, both YKL-40 and IL-6 levels in saliva and GCF had statistically significantly decreased compared with baseline values in CP patients (p < 0.001). On the other hand, no statistically significant difference was observed between 1 and 3 months in terms of salivary and GCF YKL-40 and IL-6 levels or any of the clinical findings (p > 0.016)., Conclusion: Salivary and GCF YKL-40 levels may be useful to evaluate resolution of periodontal inflammation. Within the limits of this study, YKL-40 acute-phase protein might be a potential biomarker for detection of periodontitis and monitoring the response to periodontal therapy.