The purpose of this study was to evaluate the reactions of rat subcutaneous connective tissue and bone tissue to iRoot SP, ProRoot MTA, and AH Plus. Specimens were implanted in the dorsal subcutaneous connective tissue and tibias of 36 Wistar rats. Tissue specimens were collected after rats were sacrificed at 7, 30, and 60 days after implantation. Histologic evaluations comprising inflammation severity and new bone formation were blindly made on hematoxylin and eosin-stained sections. In subcutaneous implant test, AH Plus group showed more infiltration of inflammatory cells than the other three groups at 30 days (p<0.05). In intraosseous implant test, number of inflammatory cells decreased in all groups at 7, 30, and 60 days after implantation with no statistically significant differences. Given the similar inflammatory reactions to iRoot SP and MTA, it was concluded that iRoot SP and MTA were biocompatible with the subcutaneous and intraosseous tissues of rats.