Background: Interleukine-2 is a multifunctional cytokine, considered a central regulator of host resistance against a variety of pathogens and has been recently demonstrated to exert an active role in the pathogenesis of periodontal diseases. The purpose of this study was to evaluate the effect of scaling and root planning on level of IL-2 in serum and saliva of patients with chronic generalized periodontitis, in relation to clinical parameters. Materials and Methods: A total of 50 subjects were enrolled, of which 25 had chronic generalized periodontitis and 25 periodontally healthy subjects as control. The clinical parameters included: gingival index, pocket probing depth, clinical attachment level and bleeding on probing. The level of IL-2 in serum and saliva was estimated by using enzyme linked immunosorbent assay kit at baseline and after 4 weeks of the treatment (scaling and root planning). Results: Mean IL-2 level in serum and saliva of patients with chronic periodontitis at baseline(382.15± 96.02 and 501.82± 88.08 ng/L) were significantly higher than in controls (10.98± 3.04 and 20.89 ± 7.16 ng/L; p=0.001) respectively. Post-periodontal therapy, IL-2 levels in serum and saliva increased significantly (534.18 ± 127.70 and 710.87 ± 198.15; P= 0.001.) compared to basal levels, as well as to control group (p< 0.001). Statistically significant positive association was found between salivary IL-2 level and the pocket depth in the chronic periodontitis post therapy (r = 0.45, p= 0.02). Conclusion: Short-term nonsurgical periodontal therapy leads to in a significant improvement in clinical periodontal parameters and a marked increase in IL-2 levels