Aims: This Study aimed to evaluate toxic changes that might occur in rabbit cornea after UVB exposure and possible protective role of Trehalose. Study Design: Eighteen adult white female rabbits were divided into three groups, six rabbits for each one. Group Ι received buffered saline (negative control), Group ΙΙ irradiated by UVB (positive control) and Group ΙΙI irradiated by UVB with concomitant application of Trehalose eye drops. Place and Duration of Study: Department of Pharmacology, and Department of Histopathology, Umm AL Qura University (UQU), KSA, between April 2012 and May 2012. Methodology: Eighteen rabbits were divided into three equal groups. Group Ι received buffered saline (0.9%), Group ΙΙ Only the cornea was irradiated by UVB, and Group ΙΙI were treated (by dropping trehalose three drops in each eye, six times daily) after irradiated with UVB. Two weeks after treatment, the excised corneas were employed for histopathological and immunohistochemical examinations. Results: UVB exposure induced cell death and thinning of the corneal epithelium, while the irradiated epithelium was preserved well morphologically with concomitant application of Trehalose eye drops. The irradiated corneal epithelium was significantly (P =0.026) thicker than eyes treated with Ultraviolet and Trehalose eye drops. Apoptotic cells were significantly (P =0.001) reduced in negative control and Trehalose -treated eyes than positive control eyes. Trehalose was showed to prevent oxidative stress, accelerated corneal healing, restored corneal transparency and prevent corneal neovascularization in irradiated corneas. Caspase-3, was strong significantly expressed (P