Excessive mechanical stress (MS) during hyperocclusion is known to result in disappearance of the alveolar hard line, enlargement of the periodontal ligament (PDL) space, and destruction of alveolar bone, leading to occlusal traumatism. We hypothesized that MS induces expression of osteoclastogenesis-associated chemokines in PDL tissue, resulting in chemotaxis and osteoclastogenesis during occlusal traumatism. We examined the effect of MS on relationships between chemokine expression and osteoclastogenesis using in vivo and in vitro hyperocclusion models. In an in vitro model, intermittent stretching-induced MS was shown to up-regulate the expression of CC chemokine ligand (CCL)2, CCL3, and CCL5 in PDL cells. The expression levels of CCL2 in PDL tissues, its receptor CCR2 in pre-osteoclasts, and tartrate-resistant acid-phosphatase-positive cells in alveolar bone were significantly up-regulated 4-7 days after excessive MS during hyperocclusion in in vivo rodent models. Hyperocclusion predominantly induced CCL2 expression in PDL tissues and promoted chemotaxis and osteoclastogenesis, leading to MS-dependent alveolar bone destruction during occlusal traumatism.