Background and Aim: For successful endodontic treatment Sealer is needed , and gutta-percha alone, cannot prepare hermetic seal . One of important clinical and physical characterization of sealer is setting time. This study was conducted to evaluate setting time of AH 26 , 2_Seal, Dorifill, ADSeal Meta and SDS. Materials and Methods: In this in vitro Randomized blind experimental study, sealers were AH 26, 2 Seal , Dorifill , ADSeal Meta and SDS (Iranian ZOE sealer ). Methods and material was according to ISO_6876:2001 2nd ed, "Dental Root canal Sealing Materials". 25 Samples were investigated, 5 for each group. OneWay ANOVA analysis was used by statistical specialist to show the results ( P<0.05).Results: Setting time in minutes were: AH26 = 814.2, Dorifill=93.8, 2Seal=738.4, ADSeal Meta =49.8, SDS =270.6.Conclusion: Although, all of sealers investigated here have a proper unique specification, but in conclusion and with all investigations until now, sealers with epoxy resin base, with their variety of setting time, are better sealers and can be used for different techniques, different peoples and different treatment, that needs sealers with short or long setting time.