Nicotine is the main chemical in cigarettes responsible for the tobacco's pathological effects. The influence of nicotine on bone healing remains controversial. Distraction osteogenesis provides an ideal model to study bone healing and regeneration. The present study aims to evaluate the effects of nicotine on blood perfusion, angiogenesis and bone formation using a rabbit model of mandibular lengthening. Twenty adult New Zealand white rabbits were randomly assigned to the control group and nicotine group. The total nicotine or placebo exposure time for all animals was 7 weeks. After 2- or 4-week of consolidation following osteotomy, 3-day of latency and 11-day of active distraction, the animals were sacrificed and the mandibles were harvested. Blood perfusion and vascularization were evaluated by Laser Doppler monitoring and Collagen IV immunohistochemistry staining respectively. Bone formation was assessed by radiological, histological and immunohistochemical examination. Results showed that nicotine exposure increased microvessel density, whereas inhibited blood flow and bone formation. The expression of bone morphogenetic protein (BMP)-2 in osteoblasts was also decreased. Frequent appearance of cartilage islands suggested ischemia and low oxygen tension in the distraction regenerate. We concluded that nicotine compromises bone regeneration possibly by causing ischemia and directly inhibitory effect on osteoblastic cells. Nicotine exposure enhances angiogenesis but cannot compensate for the adverse effect of vasoconstriction.