The study of host response in periodontal disease may provide a mechanism to monitor disease progression. The purpose of the present research was to determine the levels of IL-1α, IL-1β, TNF-α, IL-6, IL-6sR, IL-8, IL-10, MMP-3 and MMP-8 in gingival crevicular fluid (GCF), before and after non-surgical periodontal treatment (NSPT) in order to evaluate therapy response. Methodology: Eleven patients diagnosed with chronic periodontitis and eleven healthy subjects were selected for this study. Clinical measurements, including probing depth (PD) and clinical attachment loss (CAL) were carried out in patients diagnosed with chronic periodontitis and periodontal healthy controls. The clinical indexes evaluated were: gingival index (GI) and plaque index (PI). Samples of GCF were taken from one tooth per quadrant before and 45 days after NSPT. The levels of inflammatory mediators were measured by ELISA. Results: The values of all clinical parameters decreased significantly after treatment. The concentration levels of all cytokines and MMP-3 and MMP-8 in the GCF sample were higher in patients diagnosed with chronic periodontitis compared to the healthy group. All inflammatory mediators decreased after therapy, but did not reach control values; IL-6, Il-6sR, IL-10 and TNF-α, attained the highest reduction (70% -54%); the vales of MMP3, IL-1α, IL-1β and IL-8 were reduced between 50% - 34%; and MMP-8 showed the lowest decrease (28%). Conclusion: All clinical parameters and cytokines levels decreased after NSPT. The mediators TNF-α IL-6, IL-6sR, and IL-10 showed the largest variation between before and after NSPT and could thus be used to evaluate therapy response.