Chronic topical glaucoma therapy was reported to cause deleterious changes to the ocular surface epithelial layer. in our study we compared between changes in the ocular surface after chronic exposure to Latanoprost preserved with 0.02% benzalkonium chloride (BAK) eye drops, Travoprost preserved with sofZia eye drops and preservative-free artificial tears.Fifteen white rabbits were randomized into groups of five and received once-daily topical application of one of the three treatments for 30 days. Enucleation was performed at the end of the study. Corneal samples were processed for light and transmission electron microscopic studies and conjunctival samples for light microscopic study. Image analysis and statistical analysis of the obtained results were performed.Latanoprost eye drops preserved in BAK produced toxic changes in the form of degeneration and desquamation of the superficial epithelial cells, separation of descemet's membrane and loss of conjunctival goblet cells.Travoprost eye drops preserved in sofZia was safer and produced slight changes on rabbit's ocular surface compared with Latanoprost eye drops preserved in BAK. There were no remarkable changes after the use of travoprost when compared with the control group.It is concluded that anti glaucomatous drugs preserved with sofZia produce less ocular surface changes than those preserved with BAK.