Abstract Introduction Corneal alkali burn is one of the most severe ophthalmic emergencies that requires prompt treatment. Recently, the attention of researchers has been attracted to the use of exosomes as a novel non-cell therapy for treatment of corneal alkali burn. Aim to evaluate the possible role of mesenchymal stem cells (MSCs)-derived exosomes on healing of experimentally induced corneal alkali burn in rabbits by histological and immunohistochemical techniques. Materials and Methods Forty-five adult male New Zealand white rabbits were divided into three groups: group I (control group); group II in which corneal alkali burn was left for spontaneous healing, and group III (exosomes treated group): in which rabbits received a sub-conjunctival injection of 100 μg MSCs-exosomes after one hour from corneal alkali burn induction. Injection of exosomes was repeated every other day. All groups were further subdivided into two subgroups; subgroup A and B, where corneal specimens were collected after 7 days and 14 days, respectively. Characterization of exosomes was done using transmission electron microscope. Gross examination of the cornea was done at days 0, 1, 4,7,10 and 14. At the end of experiment, corneal specimens were collected and subjected to hematoxylin and eosin, Masson`s trichrome, periodic acid Schiff, transforming growth factor-beta and vascular endothelial growth factor immunohistochemical techniques. Histo-morphometric study and statistical analysis were also done. Results Administration of MSCs-derived exosomes in group III improved healing of corneal alkali burn by inhibiting angiogenesis and inflammation, enhancing corneal reepithelization, and providing better organization of newly formed stromal collagen fibers. Conclusion Sub-conjunctival injection of MSCs-derived exosomes could be effective in the healing of corneal alkali burn in adult rabbits.