Objectives To determine if the depth of corticotomy done with the piezoelectric knife could play a role in the intensity of the regional acceleratory phenomenon (RAP). Materials and Methods Eighteen Sprague-Dawley rats were divided into two groups: untreated (3 rats) and treatment (15 rats). In the treatment group, a split-model design was used. The right tibia received transcortical (deep) penetrations with the piezoelectric knife, while intracortical (shallow) penetrations were performed on the left tibia of the same animal. The rats were euthanized at day 1, 3, 7, 14, and 28. Cone-beam computed tomography scans were taken for each sample and then assessed by histological analysis. Results Higher amounts of osteoclastic activity and new collagen formation were observed in the deep penetration group when compared with the shallow penetration group. The former peaked at day 14 for both groups (1.53% ± 0.01% vs 0.03% ± 0.0004%, respectively), and the latter peaked at day 28 (0.65 × 106 ± 0.01 vs 0.08 × 106 ± 0.0008, respectively). Conclusions Within the limitations of this study, it appears that the intensity of the RAP in the rat is corticotomy depth dependent. This is to be kept in mind when decorticating the bone during surgically facilitated orthodontic procedures.