Adiponectin, a protein hormone produced and secreted exclusively by adipocytes, was reported to increase bone mass and stimulate angiogenesis. However, the effect of adiponectin on bone regeneration following distraction osteogenesis has not yet been reported. In this study, rapid unilateral mandibular osteodistraction (distraction rate ¼ 2 mm/day) was applied in 24 New Zealand white rabbits. The animals were then randomly divided into groups A and B (n ¼ 12 for each group). At the 1st, 3rd, and 5th day of the distraction, 200 ml PBS and 200 ml PBS contained 2 mg rh-adiponectin was intermittently injected into the distraction gap in groups A and B, respectively. At 6 weeks after the end of distraction, the rabbits were sacrificed, and the distracted mandibles were harvested and processed for radiography, dual energy X-ray absorptiometry (DXA), micro-CT, histology, and three-point bend testing. Under a rapid distraction, immature bone formation was seen in the distracted callus from group A. However, much greater bone formation and higher bone mineral density (BMD) and bone mineral content (BMC) of the distracted callus were observed in group B. Such finding was confirmed by histological, micro-CT examinations, and mechanical strength test. The results of this study suggest that intermittent administration of adiponectin can promote bone regeneration following rapid mandibular osteodistraction in rabbits. ß