Bacterial endophthalmitis is a serious complication of penetrating ocular trauma and cataract surgery. The purpose of this study is to assess the ability of an anterior chamber air bubble to prevent experimental Staphylococcus epidermidis endophthalmitis. The anterior chamber was opened with a clear corneal incision to drain the aqueous humor in one eye of 24 rabbits. S. epidermidis was injected into the anterior chamber. The infected rabbits were randomly divided into two groups. Animals in group 1 (n = 12) received an air bubble to reconstruct the anterior chamber, and animals in Group 2 (n = 12) received Balanced Salt Solution (BSS) for reconstruction. Clinical examination in each group was performed 2, 3 and 7 days after inoculation of the bacteria. Clinical examination scores were recorded. All eyes were enucleated for histophatological examination. Clinical endophthalmitis was seen in 7/12 (58.3%) in group 2, but in only 1/12 (8.3%) in group 1 (p = 0.027). Mean clinical scores of groups 1and 2 on the 3rd day were 2.6 ± 1.4 and 7.2 ± 1.7 respectively. (p < 0.001). The mean clinical scores of groups 1and 2 on the 7th day were 2.3 ± 1.2 and 6.8 ± 1.5 respectively (p < 0.001). Histopathological examination confirmed clinical findings. An air bubble in the anterior chamber may have protective effects against the development of experimental S. epidermidis endophthalmitis.