The focus of this study was to test the hypothesis that there would be no difference between the biocompatibility of cyanoacrylate-based adhesives in rat subcutaneous tissues. In total, 60 male Wistar rats were used, and divided into four groups (n = 15):Group C (control, PVA-polyvinyl alcohol sponge), Group NO (N-butyl-2-octylcyanoacrylate), Group NH (n-hexyl-cyanoacrylate), and Group EC (Ethyl-cyanoacrylate).The animals were sacrificed after time intervals of 7, 15, and 30 days and tissues were analyzed under optical microscope as regards the events of inflammatory infiltrate, edema, necrosis, granulation tissue, giant cells, young fibroblasts, and collagen formation. The results were statistically analyzed by the Kruskal-Wallis and Dunn tests (p < .05). Significant inflammatory infiltrate was shown for all the adhesives in the time intervals of 7 (p = .004) and 15 days (p = .003). In the time interval of 30 days, moderate inflammatory infiltrate was observed in Groups NH and EC, with significant difference from Control (p = .001). The quantity of collagen fibers in all the experimental groups showed significant difference compared with Control in the time intervals of 7 (p = .002) and 15 days (p = .001), at 30 days only Group EC showed a smaller quantity of collagen fibers in comparison with Control (p = .001). The hypothesis was rejected. The adhesive N-butyl-2-octylcyanoacrylate had less influence on the inflammatory intensity of multinucleated giant cells. Ethyl-cyanoacrylate demonstrated the lowest level of biocompatibility among the adhesives, but its use in clinical practice may be promising for coaptation of smaller edges of superficial tissue.Surgical adhesives were shown to be feasible for clinical use in substitution of conventional suturing. Ethyl-cyanoacrylate should be used with caution due to its greater influence on tissues. K E Y W O R D S histocompatibility, surgical, tissue adhesives