The final objective of root canal therapy is to provide complete obturation of root canal system to maintain the integrity of the attachment apparatus. The material that routinely used as root canal filling material consist Gutta- percha core with combination of sealer. Different kinds of sealers are available in the market and widely used in root canal treatment. Among this the commonly used sealers are; the material with ZOE based, with resin based, with calcium hydroxide based and glass ionomer based sealers. The purpose of this an invitro study is to evaluate the sealing ability of four root canal sealers consist of ZOE and tubliseal as zinc oxide Eugene based cement, AH26 as a resin based cement and CRCS (calciobiotic root canal sealer) as a calcium hydroxide based cement. Since in Iranian Dental Schools, pure zinc oxide powder with eugenol is commonly used as sealer, a comparative study was done to evaluate the sealingability of this cement. In this study, seventy single rooted human teeth were selected. After cleaning and shaping, the specimens were randomly divided into six groups. (4 experimental groups and 2 negative and positive groups). In experimental groups the canal were obturated with lateral condersation technique using different sealers. After obturation, the samples were cleared using Robertson method and the deepest linear apical dye penetration were evaluated by three independent evaluators. The data were analyzed by using one way analysis of variance test. The result was shown that the difference between experimental groups was not statistically significant. Whereas, the AH26 group was shown the least apical microleakage and the CRCS group were shown the most apical leakage. The result of this study was compared to the results demonstrated by others. The differences may be related to the methods of evaluation.Key words: Apical microleakage- Root canal sealers Endodontic treatment