Adiponectin (APN) has been shown to play a key role in regulating bone mineral density (BMD). Nevertheless, the effects of APN on receptor activator of NF-kappa B ligand (RANKL)-induced osteoclast formation and mechanism of regulation are not entirely clear. The study, therefore, aimed to evaluate the effect of APN on osteoclastogenesis. Our results showed that APN inhibits osteoclastogenesis and resorption function in vitro by suppressing nuclear factor-kappa B (NF-kappa B) and p38 signaling pathways, which is essential for osteoclast formation. Moreover, APN blocked the formation of F-actin rings and attenuated osteoclast-mediated bone resorptive function. Therefore, we concluded that APN may provide a potential treatment for osteoclast-related diseases, such as osteoporosis. (C) 2018 Elsevier Inc. All rights reserved.