To assess biocompatibility of any materials, animal studies are proved to be reliable. This investigation was designed to evaluate three conventinal root canal sealers (Dorifill, AB26, and Tubliseal) using subcutaneous implantation of the materials.A total of 19 mature Albinus Rats (mean weight 200 ± 25 gr) were selected in which four isolated regions were incised to implant one tube of root canal sealer in 3 regions while an empty tube was implanted in last one.Animals were sacrificed in 7, 14 and 35 days time.After histopathologic preparation, using H & E staining, vascularity and necrosis were evaluated with the thickness of the capsule, intensity, type and extension of inflammation.Results using histopathologic analysis showed that, after 14 and 35 days the thickness of capsule in Tubliseal, was higher than that of the two other sealers. However Dorifill showed a higher intesity of inflammation and necrosis compared to the two other sealers.