Background: Previous studies suggest that periodontitis is closely related to obesity and metabolic syndrome. Leptin, a pleiotrophic hormone produced by adipose tissue, has been reported to be related to periodontitis. This study investigates the effects of periodontal treatment on the serum levels of leptin and other cytokines in patients with chronic periodontitis (CP). Methods: Serum samples were taken from 33 CP patients (22 non-smokers, 11 smokers) and 18 healthy subjects. The serum leptin, adiponectin, tumor necrosis factor-a, interleukin (IL)-6, and C-reactive protein (CRP) levels were measured before and after non-surgical periodontal treatment. Results: Significant differences between healthy and CP patients were found in serum leptin, IL-6, and CRP levels (P= 0.0018, P=0.0064, and P=0.0095, respectively). The serum leptin level was associated with mean probing depth, mean clinical attachment level, mean alveolar bone loss, and body mass index. There were significant associations between serum leptin levels and 1L-6 and CRP levels. After non-surgical periodontal treatment, serum leptin, IL-6, and CRP levels were significantly decreased (mean SD before and after, P value, respectively: leptin, 8.02 +/- 5.5, 7.10 +/- 4.4, P= 0.015; IL-6, 1.73 +/- 1.02, 1.36 +/- 0.73, P=0.048; and CRP, 802.0 +/- 1065, 491.2 +/- 479.3, P=0.047). Conclusions: Periodontal treatment is effective in reducing serum leptin, IL-6, and CRP levels. The results suggest that leptin, IL-6, and CRP could be mediating factors that connect metabolic syndrome and periodontitis. J Periodontol 2010; 81:1118-1123.