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Background: Prosthodontics is impossible without denture base resins. Allergic reactions to these resins are not uncommon, albeit favorable properties. Monomeric modifications are being done to improve the properties of the material. Tricyclodecane dimethanol diacrylate (TCDDMDA) monomer has been recently identified and experimented as a comonomer with methyl methacrylate (MMA). Aim: This study aimed to investigate the histocompatibility of TCDDMDA comonomer in polymerized resin at 10% and 20% (vol/vol) concentrations in rats by histomorphometric analysis. Materials and Methods: Twenty-four male Wistar rats were randomly divided into the following four groups: NP group (control; n = 6), with no palatal appliance, Groups P0, P10, and P20 were fixed with palatal appliances fabricated of 100% MMA, 10% TCDDMDA + 90% MMA, and 20% TCDDMDA + 80% MMA, respectively. Weights of the animals were recorded just before the appliance placement and after 14 days. The animals were sacrificed, and the palatal tissues were processed for histopathological analysis. Histomorphometric parameters assessed were total epithelial (ET), connective tissue (CT), and keratin layer (KT) thicknesses. Results: No significant difference was observed regarding body weight. Group P0 showed increased ET, CT, and KT when compared to other groups. Bonferroni multiple comparison tests showed a statistically significant difference between all the groups except between P10 and P20 for all the three morphometric parameters. Conclusion: Palatal appliances with TCDDMDA comonomer showed good histocompatibility in rats up to 20% (vol/vol) concentration.