Purpose: To assess the effect of systemic administration of zoledronic acid (ZA) on mineralization of newly formed bone and to determine strain-related osteoporosis on surrounding bone during lengthening of immature rabbit mandible. Materials and Methods: Eighteen New Zealand white rabbits were divided randomly into 2 groups, and bone lengthening was carried out in the left portion of the mandible through distraction osteogenesis with a rate of 0.5 mm every 12 hours for 5 days. The experimental group was administered 0.1 mg/kg ZA intravenously. The control group was given saline infusion only during operation. All animals were sacrificed at the end of the 28-day consolidation period. The mandibles of all animals were removed and regenerate was evaluated. Osteoblasts, osteoclasts, collagen fibers, and fibroblasts were marked within 0.1-mm2 area and newly formed bone area was measured within 0.5-mm2 area. All data were analyzed using Mann-Whitney U test. Results: Although irregular bone destruction spots were seen in the control group, the experimental group showed regular ossification areas and significant difference between osteoblast and osteoclast numbers (P < .05). In the regenerate zone, there was considerable difference between the 2 groups in terms of osteoblast, osteoclast, and collagen amounts (P < .05). Additionally, newly formed bone areas and fibroblast count were higher in experimental group. Conclusions: The results of this study showed that ZA had positive effects on the new bone formation, which may potentially shorten the consolidation period. © 2008 American Association of Oral and Maxillofacial Surgeons.