Extracorporeal shock wave therapy (ESWT) has been demonstrated to accelerate bone healing; however, the mechanism underlying ESWT-induced bone regeneration has not been fully elucidated. This study aimed to examine the effects of ESWT and the process of fracture healing. A rat model of femur delayed union was established by cauterizing the periosteum. ESWT treatment at the fracture site was performed 2 weeks after the operation and the site was radiographically and histologically evaluated at weeks 4, 6, and 8. The bone union rate and radiographic score of the ESWT group were significantly higher than those of the control group at 8 weeks. Histological evaluation revealed enhanced endochondral ossification at the fracture site. The effects of ESWT on ATDC5 cells were examined in vitro. ESWT promoted chondrogenic differentiation without inhibiting the proliferation of ATDC5 cells. ESWT may induce significant bone healing by promoting endochondral ossification at the fracture site. (c) 2020 Elsevier Inc. All rights reserved.