Signaling molecules produced by osteocytes have been proposed to serve as soluble factors that contribute to bone remodeling, as well as to homeostasis of other organs. However, to the best of our knowledge, there are currently no studies investigating the role of osteocyte-secreted exosomes. In the present study, ablation of osteocytes in mice [osteocyte-less (OL)] was used to examine the microRNA (miRNA) levels of plasma-circulating exosomes. In order to investigate the function of osteocyte-secreted exosomes, exosomes derived from MLO-Y4 cells were extracted and their miRNA expression levels were examined using miRNA array analysis and deep sequencing. Comparison of miRNA expression levels between plasma exosomes from OL mouse plasma and MLO-Y4-derived exosomes revealed that decreases in the number of miRNAs from exosomes circulating in the OL mouse plasma may be caused by a decrease in secretion of exosomes from osteocytes. These results suggest that osteocytes secrete exosomes containing characterized miRNAs and then circulate in the blood, and may thus transfer their components, including miRNAs, to recipient cells where they function as signaling molecules in other organs and/ or tissues to regulate biological responses.