Background: Diabetic keratopathy is a potentially sight-threatening condition caused by epithelial and stromal disturbances, it exhibits several clinical manifestations, including persistent corneal epithelial erosions and resistant ulcers. Aim of work: to demonstrate the histological and biochemical changes in diabetic keratopathy, and to assess the effect of AgNps in healing of corneal ulcer in diabetic rat model. Material & Methods: In the current study, 55 adult male albino rats were allocated into 4 groups; group I, normal control, group II, diabetic keratopathy group, that received alloxan drug for induction of diabetes, group III, corneal ulcer group, that underwent corneal ulcer induction by NaOH solution under general anesthesia, group IV, AgNps-treated group. Cornea were extracted from each group on three time points; day 0, day 2 and day 7, and were subjected to histological, immunohistochemical and biochemical assay. Results: Diabetic keratopathy corneae showed apoptotic cellular and stromal changes, in addition to over expression of matrix metalloproteinases and growth factors. While, corneal ulcer group elicited epithelial loss, surge of the corneal tissue levels of metalloproteinases. AgNps-treated corneae showed histological improvement in corneal sections, improved apoptotic and inflammatory markers, in addition to upregulation of PI3K/AKT/MTOR signaling pathway. Conclusion: AgNps were found to be promising in improving healing of corneal ulcer in resistant conditions such as DM.