Propofol is an intravenous anesthetic and used for sedation and general anesthesia in a treatment involving invasion of the bone. Despite the period and dose of propofol being varied depending on the purpose of administration, effects of propofol on bone metabolism are less investigated. Osteoclast progenitor cells fuse with each other to differentiate into osteoclasts in the presence of receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), and osteoclasts play a central role in bone resorption during bone remodeling. In the current study, we examined the effects of both temporary and continuous propofol stimulation on RANKL-induced osteoclastogenesis. RAW264.7 cells were stimulated with 0, 10, 20, or 30 µM propofol for 5 h, 1.5 days, or 4 days in the presence of RANKL. At the end of stimulation for 5 h and 1.5 days, cells were continued to be cultured in medium containing RANKL without propofol until the end of total culture period. The expression of dendritic cell-specific transmembrane protein (DC-STAMP) and osteoclast stimulatory transmembrane protein (OC-STAMP) that are involved in the fuse of cells as well as the expression of RANK and leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), both are receptor of RANKL but have oppose effects to osteoclastogenesis are examined by real-time PCR. The formation of osteoclast-like cells was verified by tartrate-resistant acid phosphatase staining. Propofol stimulation for 1.5 or 4 days suppressed the expression of DC-STAMP, OC-STAMP and RANK, as well as the formation of osteoclast-like cells, whereas the expression of LGR 4 was increased by propofol stimulation for 4 days. These findings suggest that several hours of propofol administration do not affect RANKL-induced osteoclastogenesis. However, several days of propofol exposure may suppress the differentiation of osteoclasts due to decreased expression of DC-STAMP, OC-STAMP and RANK, as well as increased expression of LGR4.