Objective To investigate the effect of exosomes, derived from periodontal ligament cells (PLCs) under stretch loading on osteoblast differentiation, and the role of these exosomes in force-related periodontal tissue remodeling. Methods After 20% strain was applied to human PLCs cultured in vitro, exosomes from the supernatant were extracted and co-cultured with osteoblasts, then the differentiation of osteoblasts was detected, and miRNA which played a regulatory role in exosomes was explored. Results Exosomes secreted by PLCs under stretch loading could up-regulate the expression of osteogenic-related factors including alkaline phosphatase(ALP), transcription factor Osterix（osterix, Osx）, type I collagen (Col-1), Runt-related transcription factor 2 (Runx2), osteocalcin (Ocn), and bone morphogenetic protein 2 (BMP2) in osteoblasts, as well as promote osteogenic differentiation of cells. Among the miRNAs differentially expressed in PLC exosomes under stretch loading, the expression of miRNA-181d-5p was up-regulated by 107 times, and the expression of osteogenic-related factors including ALP, Osx, Col-1, Runx2, Ocn and BMP2 was also increased in osteoblasts transfected with miRNA-181d-5p. Conclusions This study preliminarily reveals the role of exosome miR-181d-5p secreted by PLCs under stretch loading in regulating the differentiation of osteoblast, which is of scientific significance for clarifying the signaling pathway in force-related periodontal tissue remodeling.