Azithromycin (AZM) have an immunomodulatory effect which decreases the GCF contents of IL-1β, IL-8 and TNF-α. The purpose of the present study was to assess the level of interleukin- 8 (IL-8) in samples of gingival crevicular fluid (GCF) from chronic periodontitis patients before and after systemic administration of azithromycin as an adjunctive treatment to scaling and root planing and to compare it with scaling and root planing alone. Materials and Methods: This study was conducted on 34 subjects divided into 10 individuals with healthy periodontium, 12 patients suffering from chronic periodontitis treated by scaling and root planing (SRP) only and 12 patients suffering from chronic periodontitis treated by SRP in conjunction with AZM, where the level of IL-8 has measured before and after non-surgical therapy, with 2 weeks and 2 months follow up. Clinical recordings (GI, PI, PD, CAL) were scored for each participant in the study before and after treatment. GCF samples were obtained from each patient included in the present study and the amount of IL-8 in the GCF samples was determined using commercially available human-specific ELISA that were in accordance with the manufacturer’s instructions (total IL-8 ELISA kit). Results: In chronic periodontitis groups either treated by SRP or SRP+AZM, all clinical parameters showed statistically significant improvement after scaling and root planing, however, there was no statistically significant difference in all clinical parameters between both groups at the end of the study. There was a statistically significant decrease in mean IL-8 level after 2 weeks and after 2 months either in patients treated with SRP or SRP + AZM. However, using AZM as an adjunct to SRP resulted in a statistical significant higher reduction in IL-8 than when using SRP alone. Concluousin: Systemic administration of AZM as an adjunctive treatment to SRP resulted in higher significant reduction of IL-8 than SRP alone.