This in vitro study was carried out to evaluate the effect of a therapeutic pressure to which the patients is subjected in the treating pressure chambers on the apical microleakage of the endodontically treated teeth sealed using either, ZOE, Silicon, and Resin based sealers. The crowns of sixty freshly extracted single rooted human teeth removed at the level of CEJ. All teeth were instrumented with a step back technique. The root canals were obturated with with a lateral compaction technique. The specimens were divided into three main equal groups of 20 roots each according to tested sealer. Each group was further divided into two subgroups according to the pressure gradients of 10 teeth each. A compression capsule was especially designed to simulate the therapeutic pressure chamber to carry out the test under normal and elevated pressure profiles. All the root surfaces were prepared for dye penetration. After removal from the dye, the roots were sectioned longitudinally into two halves. The inner gutta percha cones were removed and three methods for apical leakage evaluate were used, scanning of the inner canal wall with light scanner, digital microscope, at magnification 26X, and Digital caliper. At 1 and 2.4 bar ZOE based sealer showed the highest depth of dye penetration followed by resin based sealer while silicone based sealer recorded the lowest depth of dye penetration