During the last decade, intravital optical microscopy has launched a new trend in the field of biology. By using this advanced imaging technique we have established a new system for visualizing in situ behavior of a diversity of living cells within intact tissues and organs. Among them, we succeeded in visualizing the various dynamic phenomena within bones and joints, where various kinds of immune cells are produced and functioning although poorly analyzed by conventional methodology such as histological analyses with decalcified sections. We have so far identified the real modes of migration, differentiation and function of bone-destroying osteoclasts, special kind of macrophages responsible for bone and joint erosions. This novel technique does not only help us to understand the dynamic nature of living cells and tissues in situ, but identifies the in vivo pharmacological actions of several new drugs. Here we show our recent studies for analyzing bone-protecting actions of different biological agents treating RA by directly visualizing drug-induced cellular behaviors in vivo. Such trials would be useful for classifying various biological agents based on their respective pharmacological effects in vivo.