The aim of this study was to investigate the effect of heat shock protein 70 (HSP70) on the mRNA expression of tumor necrosis factor-alpha (TNF-α) and receptor activator of nuclear factor-kappa B ligand (RANKL) induced by compressive forces (CF) in human periodontal ligament (hPDL) cells. hPDL cells were subjected to 1.0, 2.0, or 4.0 g/cm(2) of CF for 24 h, and were treated with recombinant human inducible HSP70 for 12 h. The mRNA expression of HSP27, HSP70, HSP90, TNF-α, RANKL and OPG from hPDL cells subjected to CF was determined by real-time PCR. The protein production of HSP70 was determined by Western blot analysis and ELISA. The mRNA expression of HSP70, TNF-α and RANKL were found to be increased in a time- and magnitude-dependent manner, detectable at 12, 9, and 9 h, respectively. TNF-α and RANKL expression gradually decreased at 12 h with increasing HSP70 levels, and further decreased thereafter. Furthermore, exogenous HSP70 partially inhibited the CF-induced TNF-α and RANKL expression in a dose-dependent manner at 6 and 12 h. These results indicate that HSP70 may modulate the mRNA expression of TNF-α and RANKL in hPDL cells in response to CF.