Background and Aim: The rate of treatment success in endodontic treatment if perforation of the pulpal floor occurs, due to secondary periodontal involvement, is not satisfactory. Therefore, perforation seal plays an important role in regional repair. The aim of this study was to investigate and select a more suitable material to seal furcal perforations.Materials and Methods: In this experimental study, 70 human permanent mandibular molars with non-fused roots and intact furcal region were collected. Access openings and furcation perforations were prepared in the pulpal chamber floor. The teeth were divided into two control groups (B1-B2, negative and positive, n=5) and four experimental groups of 15 teeth in each group (A1 - A2 - A3 - A4). Group A2 was repaired with MTA, group A2 with amalgam, group A3 with Coltozol (ZOE) and group A4 was repaired with Portland cement. The access cavities of all teeth were repaired with Coltozol. Then, all samples were thermocycled for 24 hours and submerged in solution of 2% fuchsin dye for 24 hours. No cavity was prepared in negative control group. Finally, the samples were sectioned and evaluated for linear dye leakage at x25 magnification. Data were analyzed using LSD and ANOVA tests.Results: In positive control group, dye penetrated thoroughly in all perforation regions while no leakage was observed in negative control group. MTA had significantly less leakage than amalgam, Portland cement and Coltozol. The highest leakage was found in Coltozol group and the difference with amalgam and MTA was significant (P<0.01).Amalgam showed less leakage than Portland cement but the difference was not statistically significant, however; the difference between Portland cement and MTA in the amount ofleakage was significant (P<0.01).Conclusion: MTA group showed the least microleakage while Coltozol group displayed the most. In this study, the four materials were ranked as follows: MTA, Amalgam, Portland cement, Coltozol.