Perfluorocarbon liquids (PFCLs) are essential in ophthalmology due to their unique properties, such as higher density than water, inert chemical nature, and optical transparency. They serve as crucial tools in retinal detachment surgery, acting as both intraoperative aids and short-term tamponade agents. However, the interactions between PFCLs and the retinal surface are not fully understood, limiting insights into potential complications. This study investigates the interfacial interaction between perfluorodecalin (PFCL) and the retinal surface. Wetting behavior of animal retinas by water and PFCL was analyzed, revealing water droplets’ floating phenomenon in PFCL and calculating the critical radius for this effect. Dynamics of water spreading over the retina were examined. A model experiment demonstrated that water’s tendency to float over PFCL, interacting with a hydrophilic surface like the retina, could create traction and damage the retinal surface. These findings enhance our comprehension of physical processes at the PFCL/retina interface and offer practical insights for improving ophthalmic surgical procedures.