The present study aimed to investigate the effect of a compressive force (CF) on the expression of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), and vascular endothelial growth factor (VEGF) in murine osteocytes (MLO-Y4) as well as animal study. After application of a CF for 1, 3, 6, and 12 h, gene and protein expression of RANKL, OPG, and VEGF in MLO-Y4 cells were determined by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Furthermore, the effect of a stretch-activated (S-A) channel was examined by gadolinium (Gd3+) administration. In an animal experiment, the expression of these factors in osteocytes of alveolar bone was examined after experimental tooth movement in rats. After CF application, significant increases in RANKL, VEGF and RANKL/OPG ratio were shown. The upregulated gene and protein levels of these factors were reduced by Gd3+ administration. After tooth movement, upregulated RANKL and VEGF were imunohistochemically shown in osteocytes of alveolar bone. These findings suggest that CF application on osteocytes elevates expression of osteoclast-inducing factor and angiogenesis factor in vivo and vitro.