A host-derived neutrophil-activating cytokine interleukin-8 (IL-8) is secreted mainly by monocytes and is considered to be important in regulating alveolar bone resorption during tooth movement. The aim of this study was to evaluate the levels of IL-8 during mechanical forces on periodontal tissues at different stages of orthodontic therapy. Ten canine teeth of patients having different Angle classifications were selected for the study. After the premolars were extracted, the maxillary/mandibular canines were tipped distally. Gingival crevicular fluid was sampled from mesial and distal gingival crevices of each canine separately at baseline and one hour, 24 hours, six days, 10 days, and 30 days after the application of the force. An enzyme-linked immunosorbent assay for quantitative detection of IL-8 was used. Although there was an increase in the concentration of IL-8 at tension (mesial) sites after one hour, 24 hours, six days, and 10 days, a decrease was observed at 30 days. Pressure (distal) sites did not demonstrate such an increase at any period except at 10 days. However, the concentration of IL-8 at both sites showed a similar decrease and approached each other at day 30. We concluded that local host response toward the orthodontic forces might lead an increase in IL-8 and neutrophil accumulation, and this may be one of the triggers for bone remodeling processes.