Background. This experimental study sought to assess the biocompatibility of Resil, an experimental epoxy resin-based sealer, in comparison with AH26 and AH-Plus sealers in rats. Methods. Twelve male Wistar rats weighing 400 to 500 grams were evaluated in this experimental study. Four polyethylene tubes containing Resil, AH-Plus, AH26 sealers, and an empty tube were implanted subcutaneously in rats. The degree of inflammation, type of inflammatory cells present, foreign body reaction, quality of connective tissue, and presence of fibrotic capsule were evaluated histopathologically at 7 and 30 days after implanting the tubes to assess the biocompatibility of sealers. Data were analyzed using the Chi-square test. Results. At 7 days, the degree of inflammation in Resil group was almost similar to AH26 group, and 66.7% of rats showed moderate inflammation. AH-Plus group showed less inflammation than Resil and AH26 (50% of rats showed low degree of inflammation), At 30 days, the inflammatory status of all groups was the same, and 83.3% of rats showed very low degree of inflammation. The inflammatory response during the experiment decreased from day 7 to day 30 in all groups. The neutrophil count (P=0.00), fibrotic capsule (P=0.01) and the amount of granulation tissue (P=0.05) significantly decreased from day 7 to day 30 in Resil group. Conclusion. Resil sealer showed appropriate biocompatibility at 7 and 30 days after subcutaneous implantation in rats, comparable to AH26 and AH-Plus. Clinical studies are required to confirm these results.