The reaction of subcutaneous tissues to Endofill, Endomethasone, Sealer 26, and AH-Plus was investigated microscopically after implantation of in rats polyethylene cannulae, obturated with gutta-percha cones and sealers, in rats. Empty polyethylene cannulae and cannulae filled with gutta-percha cones alone were used as controls. The inflammatory reactions caused by the sealers were evaluated 7, 14, and 30 days after implantation using a descriptive, histopathological analysis. Inflammatory reactions at each implant site were gauged as either absent, discreet, moderate, or intense, and scores from 0 to 3 were attributed, respectively. Microscopic analysis revealed that Endomethasone showed the best biological behavior for all postimplant periods, followed by Sealer 26 and AH Plus, which produced an irritating effect only during the initial pos-implant period. Endofill caused the severest irritation, producing an inflammatory reaction that ranged from moderate to intense over the entire experimental period. Reactions were more intense near those parts of the cannulae containing more sealer. These results reveal that the root canal sealers tested cause inflammation in rat, subcutaneous conjunctive tissue, the intensity of which may be related to the type and quantity of sealer used, and to postimplant period.