Osteocytes, which are the most abundant cell type in bone, regulate osteoblasts and osteoclasts via both cell–cell interactions and paracrine signaling, and osteocyte-derived exosomes might contribute to this paracrine action. In this study, we investigated the effects of osteocyte-derived exosomes on regulating osteoblasts and osteoclasts and studied the potential mechanism. Materials and Methods: Osteocyte-derived exosomes were extracted and identified. PKH67-labeled exosomes were incubated with MC3T3-E1 cells and RAW264.7 cells, and fluorescence confocal microscopy was used to analyze the uptake of exosomes. ALP stain- ing and TRAP staining were used to analyze osteoblast activity and osteoclast formation. The level of miR-214-3p in exosomes was analyzed by qPCR and the incorporation of FAM-labeled miR-214-3p from exosomes into MC3T3-E1 cells was evaluated. The expressions of ephrinA2 and RANKL in exosomes were studied. Results: Our results demonstrated that osteocyte-derived exosomes might recognize osteoblasts through the ephrinA2 protein; thus, miR-214-3p in exosomes was transferred into osteoblasts to inhibit osteoblast activity. Meanwhile, we found that osteocyte-derived exosomes could be transferred into osteoclasts to induce osteoclast formation by releasing RANKL. Conclusion: These findings suggest that osteocyte-derived exosomes play an important role in the regulation of osteoblast and osteoclast activity, which might occur via miR-214-3p and RANKL.