OBJECTIVE To compare the rate of epithelial healing of corneal erosion in an animal model with 2 commercial formulations of fourth-generation fluoroquinolones: 0.3% gatifloxacin and 0.5% moxifloxacin. METHODS Corneal erosions, 6 mm in diameter, were created in 28 rabbit eyes. The rabbits were randomized to receive topical gatifloxacin, moxifloxacin, or nonpreserved saline. Drops were administered every 15 minutes for 1 hour, then hourly for 3 hours, and then 4 times daily until the erosion reepithelialized. Eyes were examined with fluorescein drops and photographed every 12 hours with a cobalt blue-filtered light. When reepithelialization was observed, the rabbits were euthanized, and their eyes were enucleated for histopathologic evaluation. RESULTS Reepithelialization of the corneal erosions was fastest in the saline-treated eyes (57.3 +/- 8 hours), followed by moxifloxacin (62.7 +/- 11.7 hours) and gatifloxacin (66 +/- 8.5 hours). These differences in the time to closure of the erosions among the 3 groups were not statistically significant. Although significant differences were found among the healing progression curves when all 3 groups were compared (P = 0.042), the difference between the 2 antibiotic-treated groups was not significant. CONCLUSIONS Only slight differences in epithelial healing rates were found between the gatifloxacin-, moxifloxacin-, and saline-treated groups, suggesting that the 2 fluoroquinolones may have an equivalent role as prophylactic treatment of trauma- or surgery-induced corneal erosions.