Antifibrinolytic agents, epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), have been reported to be efficacious in the treatment of chronic persistent epithelial defects. Within the regulatory mechanism of corneal reepithelialization, fibronectin serves as a primary adhesive component in the healing process and anchors regenerating epithelial cells to underlying stroma. EACA and TXA inhibit the activation of plasmin thereby decreasing plasmin-induced catabolism of fibronectin. In this study, acute reepithelialization following treatment with EACA and TXA was evaluated in the cultured rat cornea model. Sprague Dawley rat corneal explants with 3 mm corneal defects, induced with 1 N NaOH, were cultured with either EACA or TXA. After 12 or 24 hr incubation periods, corneal explants were stained with bromodeoxyuridine stain for measuring cellular division and migration or Trypan Blue for measuring the extent of dead cells. Both EACA and TXA increased the rate of reepithelialization in comparison to an untreated control. EACA was up to 35% more efficacious than TXA. Thus, this study demonstrated an acute effect for EACA and TXA versus the previously reported efficacy of chronic therapy required for persistent epithelial defects. Broad applications may prove beneficial in the clinical treatment of corneal abrasions, persistent corneal epithelial defects, or alkali burns.