The working mechanism of bisphosphonate on bone cellsis unclear despite its powerful inhibitory activity on boneresorption. The differentiation and activation of osteoclastsare essential for bone resorption and are controlled by thestimulatory RANKL and inhibitory OPG molecules. Teethexhibit a range of movement patterns during their eruptionto establish their form and function, which inevitably accompaniesperipheral bone resorption. Hence, the mandible,which contains the teeth during their eruption processes, isa good model for revealing the inhibitory mechanism ofbisphosphonate upon bone resorption. In the present study,RANKL and OPG expression were examined immunohistochemicallyin the mandible of rats with developing teethafter alendronate administration (2.5 mg/kg). The preeruptivemandibular first molars at postnatal days 3 to 10showed the developing stages from bell to crown. Nomorphological changes in tooth formation were observedafter alendronate administration. The number of osteoclastsin the alveolar bone around the developing teeth decreasedmarkedly at postnatal days 3, 7 and 10 compared with thecontrol group. RANKL induced strong positive immunohistochemicalreactions in the dental follicles and stromalcells around the mandibular first molar. In particular, manyosteoclasts with strongly positive reactions to RANKLappeared above the developing mandibular first molars atpostnatal days 3 and 10. Immunohistochemical reactionswith RANKL after alendronate administration were weakerthan the control groups. However, the immunohistochemicalreactivity to OPG was stronger after alendronate administration,at postnatal days 3 and 10. These results suggestthat alendronate may decrease bone resorption byregulating the RANKL/OPG pathway in the process ofosteoclast formation, resulting in a delay in tooth eruption.