Osteoclasts play critical roles not only in normal bone homeostasis ('remodeling') , but also in the pathogenesis of bone destructive disorders such as osteoporosis, rheumatoid arthritis, and bone metastasis. However, it has not been known how osteoclast precursor monocytes migrate into the bone surface and what controls their migratory behaviors. To reveal these systems, we have recently established a new system for visualizing intact bone tissues and bone marrow cavities in live animals by using an advanced imaging technique with intravital two-photon microscopy. By means of the system we have revealed that sphingosine-1-phosphate (S1P) , a lipid mediator, dynamically regulates migration and localization of osteoclasts and their precursors in vivo . Here we show the latest data and the detailed methodology of intravital imaging of bone tissues, and also discuss its further application.