【Background and Purpose】Management of chronic diabetic and ulcers require multidisciplinary approaches including diabetic control, wound care, antibiotic, shoe wear off loading, and surgery in selected cases. The results are inconsistent and irregular, and most studies reported unsatisfactory results. Many adjunctive therapies are implemented in the care of chronic skin ulcers including hyperbaric oxygen therapy (HBO), ultrasound, recombinant human platelet-derived growth factor-BB (rPDGF-BB), vacuum assisted wound closure (VAWC) and acellular matrix. HBO is the most commonly utilized at our institution. Mixed results of HBO in chronic skin ulcers are reported. Several studies reported the beneficial effects in chronic skin ulcers, but none showed universal success. Therefore, the development of a new effective method of treatment for chronic skin ulcers is extremely valuable. Wang et al demonstrated that extracorporeal shockwave acts as mechanotransduction that produces the therapeutic benefits through complex biological pathways including neovascularization and tissue regeneration. Gerdesmeyer et al showed bacteriostatic effects of shockwave in experiments. Schaden et al reported the effectiveness of extracorporeal shockwave in acute and chronic soft tissue wounds. Saggini et all reported effectiveness of ESWT in chronic skin ulcers with 50% completely healed within 6 sessions of treatment. However, no working mechanism of ESWT was discussed. With this background, it appears that extracorporeal shockwave may be effective in the treatment of chronic diabetic ulcers. We have conducted a pilot study using orthowave 180 (TRT, Woodstock, GA) in the treatment of chronic ulcers. The preliminary results of a pilot study in 26 patients with 31 ulcers showed healed or >50% improved ulcers in 90%, 10% unchanged and none worse. The results of the pilot study was published by the Journal of Surgical Research 2009; 152: 96-103. The poster exhibit of this study won the 1st place award in the category of tumor and metabolism of the 75th AAOS annual meeting in San Francisco, CA in March 2008. This study continues the research using derma-PACE (derma-pulse acoustic cellular expression). Derma-PACE (Sanuwave, Alpharetta, GA) is a new shockwave device designed for the treatment of diabetic ulcers. The purpose of this study is to evaluate the efficacy and safety of Derma-PACE shockwave device in the treatment of chronic diabetic ulcers, and to compare the results with that of hyperbaric oxygen therapy, and to investigate the blood flow perfusion, histopathological examination and immunohistochemical analysis.