Angiogenesis plays an important role during bone regeneration. Low-intensity pulsed ultrasound (LIPUS) has been proven to accelerate the process of bone fracture healing. However, the mechanism of the effect of LIPUS on bone regeneration is still unclear. In the present study, we used human umbilical vein endothelial cell (HUVEC) and human osteosarcoma cell (MG-63) to investigate the effect of LIPUS stimulation in an endothelial cell–osteoblast coculture system. At the same time, we used transwell and in vitro angiogenesis assay to observe how LIPUS affects endothelial cells. The results demonstrated that LIPUS could significantly increase the migratory ability and promote tube formation in angiogenesis of HUVECs. Furthermore, LIPUS could significantly elevate the expression of osteogenesis-related genes on osteoblasts such as Runt-related transcription factor 2, alkaline phosphatase, Osteorix, and Cyclin-D1, indicating the pro-osteogenesis effect of LIPUS in our coculture system. In conclusion, endothelial cell is involved in LIPUS-accelerated bone regeneration, the positive effect of LIPUS may be transferred via endothelial cells surrounding fracture healing site.