The present study aimed to determine whether the mitogen‑activated protein kinase (MAPK) signaling pathway is involved in the osteoprotegerin (OPG)‑mediated inhibition of osteoclast differentiation and maturation. RAW264.7 cells were incubated with macrophage colony‑stimulating factor (M‑CSF) and receptor activator of nuclear factor‑κB ligand (RANKL) to stimulate osteoclastogenesis and treated with various concentrations of OPG, an inhibitor of osteoclast differentiation. The differentiation and activation of osteoclasts were monitored by tartrate‑resistant acid phosphatase staining and bone resorption assays. The phosphorylation levels of p38‑MAPK, c‑Jun N‑terminal kinase (JNK)‑MAPK and extracellular signal‑regulated kinase (ERK)‑MAPK in the different treatment groups were determined by western blot analysis. The results confirmed that M‑CSF + RANKL stimulated the differentiation and activation of osteoclasts as well as the phosphorylation of p38‑MAPK, JNK‑MAPK and ERK‑MAPK in osteoclasts, which was attenuated by OPG treatment. These findings indicated that the MAPK signaling pathway is involved in the regulation of osteoclastogenesis and in the OPG‑mediated inhibition of osteoclast differentiation and activation.