This study investigated the potential toxic effects of air on primary human retinal pigment epithelial (RPE) cells in vitro. Clinically during pars plana vitrectomy air is used as either a temporary tamponade during air-fluid exchange or mixed with gas to provide an internal tamponade in the postoperative period lasting several days or weeks. The study showed that the RPE cells revealed large deformities after six hours of air exposure. They observed a more flattened, hypertrophic shape and a decrease in cell viability after 12 hours of exposure. Although during retinal surgery the RPE is not directly exposed to air, other animal studies have reported toxicity to the inner limiting membrane, nerve fibre layer and retinal ganglion cells. The obvious limitation to this study is that the model was not dynamic and not in vivo, however, it showed similar results to animal studies using cell culture models. Further studies are necessary in order to fully explore and apprehend the possible toxic effect of air on human retinal epithelium.