Abstract OBJECTIVE: This study evaluated, histopathologically, the pulpal and periapical response to a silorane-based resin (Filtek Silorane) and a methacrylate-based nanoparticle resin (Filtek Supreme XT) in deep cavities in dogs, having zinc oxide and eugenol-based cement (ZOE) as a control. METHODS: The tooth/bone blocks were collected after 10 and 90 days and processed for microscopic analysis of the dentin, pulp, and periapical tissues using a score system. Data were analyzed statistically by Kruskal-Wallis and Dunn post-test (α=0.05). RESULTS: At 10 days, the pulp, connective tissue, and periodontal ligament showed normal characteristics. No resorption areas were observed. Both resins caused significantly less (p<0.05) periapical and pulpal inflammatory response than ZOE. At 90 days, for all materials, the connective pulp tissue was healthy and dense, with a normal blood vessel system. The apical and periapical region had normal structure and thickness. CONCLUSIONS: The use of the Filtek Silorane and the Filtek Supreme XT resins caused no adverse pulpal and periapical reactions after restoration of deep dentin cavities in vivo.