BACKGROUND The composition of the root canal filling materials together with the apical limit of the root canal obturation affect the complete periapical healing after root canal therapy. OBJECTIVE This study was performed to evaluate and compare the periapical healing in response to calcium-silicate (iRoot SP) and calcium-hydroxide (Apexit) based-sealers. METHODS Seventy-two upper premolars root canals of six dogs were used. The teeth were randomly assigned to four groups: Group one: roots were obturated using gutta-percha and Apexit-sealer; Group two: roots were obturated using gutta-percha&iRoot SP-sealer; Group three: the teeth were left open without obturation; Group four: where healthy teeth were used as a negative control. Teeth were evaluated after one, two and three months. The newly formed mineralised apical tissue and the periapical inflammatory infiltrate of the obtained photomicrographs were evaluated, and scorings were statistically-analysed. RESULTS The mean percentage of the periapical inflammatory infiltrates and mineralisation scoring after one, two and three months evaluation period were not significantly different among the four groups (P > 0.05). CONCLUSIONS Regardless of the sealer used, iRoot SP and Apexit promote healing of periapical tissues. IRoot SP sealer showed early insignificant more partial and almost full healing after two and three months.