Estrogen deficiency has been proposed as a risk factor for alveolar bone loss, but whether or not estrogen will influcence the bone rebuilting process during orthodontic tooth movement and what the mechanisms involved remain unclear. The paper aims to provide new information that may elucidate the modulatory effect of estrogen on the bone-resorbing cytokines RANKL and its anti-resorptive factor OPG secrected by HPLFs which are already force-stimulated. The expression of OPG mRNA is rising after mechanical loading either with or without stimulated by estrogen before. But HPDL cells exposured to estrogen for 24 h before loaded tend to express more OPG mRNA. Compared with the no-estrogen group, the inhibit trend of RANKL mRNA is much more apparent in with-estrogen group. Moreover, estrogen and mechanic force time-dependently increased OPG expression and attenuated the RANKL expression. Estrogen deficiency has been proposed as a risk factor for alveolar bone loss, but whether or not estrogen will influcence the bone rebuilting process during orthodontic tooth movement and what the mechanisms involved remain unclear. The paper aims to provide new information that may elucidate the modulatory effect of estrogen on the bone-resorbing cytokines RANKL and its anti-resorptive factor OPG secrected by HPLFs which are already force-stimulated. The expression of OPG mRNA is rising after mechanical loading either with or without stimulated by estrogen before. But HPDL cells exposured to estrogen for 24 h before loaded tend to express more OPG mRNA. Compared with the no-estrogen group, the inhibit trend of RANKL mRNA is much more apparent in with-estrogen group. Moreover, estrogen and mechanic force time-dependently increased OPG expression and attenuated the RANKL expression.