Objective: The aim of this study was to estimate the levels of Leptin and TNF-α in serum and gingival crevicular fluid, in patients with chronic periodontitis(CP), before and after phase I therapy.   Patients and Methods: A total of thirty subjects were included in this study; 20 CP patients (group I)   and 10 systemically healthy subjects with clinically healthy gingiva as a control group (group II). The nonsurgical periodontal therapy was done in group I. Periodontal parameters, including PI, GI, BOP, PD and the CAL, were recorded. GCF and serum were collected from all individuals included in the study; the first sample was collected from all groups (study and control) before phase I therapy. The second sample was collected 4 weeks after phase I therapy from group I. Levels of Leptin & TNF-α in GCF and serum were quantified using ELISA. The results: - showed a statistically significant reduction in total levels of leptin & TNF-α in serum and TNF-α in GCF in study group after phase I therapy. In contrast, leptin levels in GCF of study group showed a significant increase after phase I therapy.  Results also showed all clinical parameters were significantly improved after the phase I periodontal therapy in groups I  (p < 0.001).  Conclusions:Scaling and root planing (SRP) is the mainstay of treatment of periodontal diseases as SRP was effective in improving clinical parameters in CP patients. Leptin level & TNF-α in serum is reduced after phase I therapy.TNF-α in GCF is reduced after phase I therapy while leptin level in GCF is increased after phase I therapy.