PURPOSE: To investigate the effects of topical human platelet lysate (HPL) on exposure keratopathy (EK) in a rabbit model, with a focus on its anti-inflammatory and anti-dehydration properties on the cornea. METHODS: Short-term exposure keratopathy was induced in New Zealand albino rabbits by keeping the eyelids open for four hours, followed by eyelid closure for another four hours, during which the treatment was applied. HPL, fetal bovine serum (FBS), or preservative-free artificial tears (PFAT) were administered every 15 minutes, and corticosteroid was applied every one hour during the treatment period. Corneal thickness changes and epithelial defects were assessed using anterior segment optical coherence tomography (AS-OCT) and fluorescein staining. In vivo confocal microscopy (IVCM) was used to evaluate inflammatory cell infiltration, whereas immunohistochemistry (IHC) was performed to confirm the presence of CD8+ T cells, neutrophils, and macrophages and the cell proliferation marker Ki67. RESULTS: After completing the treatment, no significant difference in fluorescein staining was observed among the four groups. However, AS-OCT revealed more effective recovery of corneal thinning in the HPL- and FBS-treated groups, including improvements in epithelial, stromal, and total corneal thickness. IVCM revealed significantly reduced infiltration of inflammatory cells in the HPL-, FBS-, and corticosteroid-treated groups compared to the PFAT-treated group across the central cornea, peripheral cornea, and conjunctiva. IHC for CD8+ T cells, neutrophils, and macrophages showed similar findings. HPL-treated groups showed more Ki-67-positive cells compared to the PFAT- and corticosteroid-treated groups. CONCLUSIONS: HPL treatment effectively reduced inflammation, promoted the recovery of corneal thickness, and induced cellular proliferation after dehydration, demonstrating its potential as a treatment for EK.