During orthodontic tooth movement, mechanical stresses induce inflammatory reactions in the periodontal ligament (PDL). We hypothesized that chemokines released from PDL cells under mechanical stress regulate osteoclastogenesis, and investigated the profiles and mechanisms of chemokine expression by human PDL cells in response to mechanical stress. In vitro, shear stress and pressure force rapidly increased the gene and protein expressions of IL-8/CXCL8 by PDL cells. Consistently, amounts of IL-8 in the gingival crevicular fluid of healthy individuals increased within 2 to 4 days of orthodontic force application. The PDL cells constitutively expressed low levels of IL-1β, which were not further increased by mechanical stress. Interestingly, neutralization of IL-1β abolished IL-8 induction by mechanical stresses, indicating that IL-1β is essential for IL-8 induction, presumably though autocrine or paracrine mechanisms. Finally, experiments with signal-specific inhibitors indicated that MAP kinase activation is essential for IL-8 induction.