0.05% cyclosporine A eye drops is a kind of new medication for dry eye after corneal refractive surgeries. However, it is still unclear how this eye drops affect the healing process of corneal epithelial defects caused by operative procedures. In this vivo study, the effect of 0.05% cyclosporine A eye drops on the healing process of the corneal epithelium was assessed in a rat model featuring mechanically induced central corneal epithelial defects. These Sprague-Dawley rats were randomly divided into three groups, the 0.05% cyclosporine A eye drops group (CsA group), the 0.1% sodium hyaluronate eye drops group (HA group), and the model control group (MC group). The epithelial healing, tear secretion, epithelial microvilli, expression of apoptosis markers (TUNEL, p53, and bcl-2 proteins), inflammatory factors (IL-1β, TNF-α, and IL-6), and epidermal growth factor (EGF) were detected in the current study using corneal fluorescein sodium staining, phenol red thread test, transmission electron microscopy (TEM), immunofluorescence, and enzyme-linked immunosorbent assay (ELISA), respectively. Compared to the other two groups, lower expression of apoptosis markers and inflammatory factors were exhibited in the CsA group, along with its faster and better epithelial healing and higher tear secretion (P < 0.05). In conclusion, 0.05% cyclosporine A eye drops effectively promote the healing process for corneal epithelial defects in rats, potentially offering advantages for rapid corneal recovery after refractive surgical procedures.Copyright © 2024. Published by Elsevier Ltd.