Abstract This study compared the effect of systemic and local administration of alendronate on distraction osteogenesis in rabbit mandibles. Thirty New Zealand white rabbits were allocated to 3 groups: 10 rabbits for systemic alendronate; 9 for local alendronate; and 11 as controls. After a 5 day latency period, distraction was performed at a rate of 0.8 mm/day for 9 days via a custom-made distractor. Animals were killed at the end of the consolidation period of 28 days. The distracted mandibles were harvested and evaluated by plain radiography, computed tomography (CT), dual energy X-ray absorptiometry (DEXA), and histomorphometry. Histologically, comparing the systemic and local alendronate groups, there were no statistically significant differences in the bone healing parameters, but each group showed a statistically superior effect over the control group ( p < 0.05). Quantitative CT evaluation showed a significant difference mean in the density of the regeneration between experimental and control groups. There was a significant increase in mean bone mineral density in the experimental groups compared with the control group. Histologic, CT, and DEXA analysis demonstrated that using systemic and local alendronate may be effective in accelerating new bone formation in the distraction gap in rabbit mandibles.