As zirconia is today probably the dental material with the largest increase in the frequency of use in dental prosthetics, the reason for this study was based on a series of clinical observations made following its use in clinical prosthetics. Thus, we were interested in two aspects: the histological evaluation of the response of the oral soft tissues to the presence of the prosthetic structures in zirconia, and the microscopic evaluation of the abrasion lesions that appeared in the hard dental tissues of the zirconia prostheses antagonists. For the first part, samples from three zirconia-based dental prosthetics commercial products were implanted submucosal in the oral cavity of male Wistar rats. After six weeks, the oral soft tissue reaction was clinically and then histologically investigated. For the second part, we made two study groups to investigate the influence of the zirconia-glazed surface vs. polished surface to the wear pattern of the antagonist enamel, using a tribological equipment and a dedicated software. Our study showed a good clinical response of the oral soft tissues surrounding the inserted zirconia samples, with subclinical, only histological revealed, signs of inflammation, of a foreign body reaction, while polished zirconia samples determined abrasion surfaces, with a different pattern and significantly smaller dimensions, compared to zirconia glazed samples, at the level of the hard dental tissues of the antagonist teeth. Despite the generally good response of the biological structures to the presence of zirconia prosthetic structures in the oral environment, more scientifically proved information is needed to obtain the desired biological responses in all clinical situations.