Osteoclasts, multinucleated bone‐resorbing cells, are specialized cells derived from the monocyte/macrophage lineage. Therefore, it is essential for mononuclear precursors to find a fusion partner during its differentiation. Our previous study showed an important role of cell communication via Mac‐1 (CD11b/CD18) during osteoclastogenesis. However, the counter receptor of Mac‐1 was still unknown. Flow cytometric analysis showed that bone marrow‐derived mononuclear cells, used as osteoclast precursors, expressed intercellular adhesion molecule‐1 and ‐2. Quantitative RT‐PCR analysis revealed that expression level of ICAM‐2 was higher than that of ICAM‐1 in bone marrow cells. The osteoclastogenesis induced by receptor activator of NF‐kappaB ligand (RANKL) was inhibited by anti‐ICAM‐2 neutralizing antibody but not by anti‐ICAM‐1 neutralizing antibody. The inhibitory effect of anti‐ICAM‐2 antibody on osteoclastogenesis was enhanced by simultaneous treatment of anti‐CD11b neutralizing antibody. Furthermore, osteoclastogenesis induced by tumor necrosis factor α (TNFα) was also inhibited by anti‐ICAM‐2 neutralizing antibody. The involvement of lymphocytes in osteoclastogenesis was excluded, because anti‐ICAM‐2 antibody inhibited osteoclastogenesis using bone marrow‐derived cells from immunodeficiency mice. Immunocytochemical staining demonstrated colocalization of ICAM‐2 and Mac‐1 during osteoclastogenesis; however, Mac‐1 immunoreactivity was lost in differentiated multinucleated osteoclast. These results suggest the important role of ICAM‐2/Mac‐1 binding in osteoclastogenesis induced by either RANKL or TNFα.