The aim of this study is to evaluate in humans whether the Regional Acceleratory Phenomenon (RAP) resulting from micro-osteoperforations (MOPs) performed with Propel® can be histologically demonstrated, supporting the ability of this technique to accelerate orthodontic movement. The study included six patients (2 M, 4 F; aged between 23 and 74 years) with edentulous areas requiring implant rehabilitation. These edentulous areas were micro-osteoperforated with Propel®. 15-30 days later, a biopsy was performed in the stimulated areas and in non-stimulated control areas. Classical histological analysis, quantitative histological analysis, and histomorphometric analysis were performed on 12 bone biopsies (6 “stimulated” and 6 “non-stimulated”). Non-stimulated” samples revealed normal compact bone surrounded by normal lamellar structure without evidence of significant remodeling activity. “Stimulated” samples 1-3-4 showed increased irregularity in the lamellar structure, with no additional alterations; 2-5-6 exhibited marked bone structure remodeling with increased osteocytes, chronic inflammatory infiltrate, and neovascularization of intertrabecular spaces. In this pilot study conducted for the first time on humans, MOPs performed with Propel® induced the RAP reaction in 50% of the samples. Chronological age may influence the reactivity of the response to corticotomy.