The ideal biomaterial used in endodontics in the process of sealing the radicular canals should possess a group of qualities for a predictable outcome: biocompatibility, initiation of ontogenesis and cementogenesis, ease of handling, sufficient manipulation time, and convenient price. For a perfect sealing, the root canal treatment can be followed by prosthetic restoration. This study of biocompatibility aims to determine the quantification of the local reaction following the implantation of three biomaterials in the rabbit subcutaneous connective tissue. The used biomaterials with particular reparative properties are: MTA (Mineral Trioxide Aggregate, Dentsply, Tulsa Dental, Johnson City, TN, USA), Sealapex (Kerr, Switzerland), and DiaRoot BioAggregate (Innovative BioCaramix Inc, Vancouver, BC, Canada). The first two biomaterials (MTA, Sealapex) are already being used in endodontic treatments, and the latter was newly introduced during the concrete development of the study. This is an experimental study focused on qualitative and quantitative analysis based on histopathological examination and underlined by the positive result of the study undertaken of the applicability of oral rehabilitation treatments, increasing patients’ quality of life by a significant proportion of 95%, and generating optimal functionality of the stomatognathic system with prosthetic devices as well as accomplishing the objectives of homeostasis.