This study assessed influence of 1% phytic acid and 17% ethylenediaminetetraacetic acid (EDTA) on the dentinal tubules penetration of EndoSequence BC bioceramic-based and AH Plus resin-based sealers using confocal laser scanning microscopy (CLSM). Forty single-rooted mandibular premolars were divided randomly into four groups (n = 10). Group 1 received final irrigation with 1% phytic acid solution and canals sealed by AH Plus sealer, Group 2: 1% phytic acid solution and EndoSequence BC sealer, Group 3: 17% EDTA solution and AH Plus sealer and Group 4: 17% EDTA solution and EndoSequence BC sealer. Specimens were horizontally sectioned 2, 4 and 6 mm from the apex. Average maximum depth of sealer penetration was examined using CLSM. Group three showed the deepest sealer penetration at all three levels which was significantly higher than all other groups (P ˂ 0.05). Deep sealer penetration is achievable with AH Plus and EDTA. Phytic acid groups have moderate tubular penetration ability.