||Delivering macromolecules to the posterior segment of eye non-invasively is always challenging as the eye has several barriers to protect it from being invaded. The barriers can be summarized into dynamic, static and metabolic barriers. These barriers prevent the macromolecules from penetrating the target site of most posterior diseases, the macula. Although therapeutics for treating posterior segment diseases are being developed, no safe or effective delivery methods are available. Considering the route of delivery, the transscleral route could be a potential route for delivering macromolecule to the posterior segment, as it is closer to the target site. In this project, low power, medium frequency ultrasound (1MHz, 0.5W/cm2) was applied on the equator of the eye ex vivo for a short duration. A fluorescein conjugated albumin sized 66kDa was used as the model protein for investigation. The diffusivity of the albumin in the sclera was increased by 1.5 fold from 3.77 × 10‐8 cm2/sec to 5.58 × 10‐8 cm2/sec. The increased permeability of the sclera was found to be temporary with the barrier function was restored after 15 minutes. The ultrasound treatment did not seem to cause retina detachment or deformation of the retinal layer at the area of the treated zone. Based on the experimental observation, we deduce that the barrier property of the sclera is altered due to inertial cavitation but not thermal effects and ultrasound-induced convection. This report demonstrates the feasibility of enhancing the macromolecule delivery into the sclera by ultrasound.