Despite the success in clinical application, the exact mechanism of shock wave therapy remains unknown. We hypothesized that shock wave therapy induces the ingrowth of neovascularization and improves blood supply to the tissues. The purpose of this study was to investigate the effect of shock wave therapy on neovascularization at the tendon-bone junction. Fifty New Zealand white rabbits with body weight ranging from 2.5 to 3.5 kg were used in this study. The right limb (the study side) received shock wave therapy to the Achilles tendon near the insertion to bone. The left limb (the control side) received no shock wave therapy. Biopsies of the tendon-bone junction were performed in 0, 1, 4, 8 and 12 weeks. The number of neo-vessels was examined microscopically with hematoxylin-eosin stain. Neovascularization was confirmed by the angiogenic markers including vessel endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expressions and endothelial cell proliferation determined by proliferating cell nuclear antigen (PCNA) expression examined microscopically with immunohistochemical stains. The results showed that shock wave therapy produced a significantly higher number of neo-vessels and angiogenesis-related markers including eNOS, VEGF and PCNA than the control without shock wave treatment. The eNOS and VEGF began to rise in as early as one week and remained high for 8 weeks, then declined at 12 weeks; whereas the increases of PCNA and neo-vessels began at 4 weeks and persisted for 12 weeks. In conclusion, shock wave therapy induces the ingrowth of neovascularization associated with early release of angiogenesis-related markers at the Achilles tendon-bone junction in rabbits. The neovascularization may play a role to improve blood supply and tissue regeneration at the tendon-bone junction.