Introduction and objectives: One of the essential phases of root canal treatment is root canal obturation. Solid or semi-solid materials are the most common obturating materials (paste or softened form). Sealer is a biomaterial that enables the sealing process to be carried. This study aimed to evaluate the inflammatory response to Adseal sealer and Sure-Seal Root sealer in rats. Materials and methods:This experimental study was conducted on 28 Wistar rats that were divided into four groups of seven animals per group based on four time periods (7, 14, 30 and 60 days). Each rat received subcutaneous implants containing Adseal sealer (Meta Biomed, Cheongju, Korea) and Sure-Seal Root sealer (Sure Dent Corporation, Gyeonggi-do, South Korea) tubes as well as an empty tube as a control. After the insertion of the tubes, the first to fourth groups were sacrificed on days 7, 14, 30 and 60, respectively, by injecting a high dose of anesthetics. Subsequently, the histopathologic features of the samples were investigated. Data were analyzed in SPSS software (version 26) using Freidman, Wilcoxon, Kruskal-Wallis and Mann-Whitney U tests. A p-value less than 0.05 was considered statistically significant. Results:On day 7, the severity of inflammation was higher in the Adseal sealer and Sure-Seal Root sealer groups compared to the control group. Moreover, on day 14, the level of inflammation was higher in the Sure-Seal Root sealer group than the Adseal sealer and control groups. In addition, on days 30 and 60, the severity of inflammation was similar in both the case and control groups and decreased in all samples. Formation of granulation tissue was observed in all samples on day 14. There was fibrosis tissue in the Sure-Seal Root sealer samples (71.4%) on day 60; however, no fibrosis tissue was observed in the Adseal sealer and control groups. Conclusion:It is concluded that the Sure-Seal Root sealer might lead to a more inflammatory response compared to the Ad Seal sealer. However, due to decreasing inflammation in sealers over time, both sealers are biocompatible.