Purpose.Lomefloxacin was evaluated as a potential topical therapy for bacterial keratitis.Methods.Lomefloxacin was compared with ciprofloxacin in different rabbit keratitis models. A total of 216 corneas were infected withStaphylococcus aureus(ciprofloxacin-susceptible and -resistant),Streptococcus viridans,Streptococcus pneumoniae,Pseudomonas aeruginosa, and Serratia marcescens and were treated with lomefloxacin (0.3%), ciprofloxacin (0.3% Ciloxan), and the control phosphate-buffered saline (PBS), respectively. The data were analyzed statistically comparing the decrease in the number of recovered viable bacteria.Results.Compared with PBS-treated control corneas, the colony counts for all bacterial isolates were significantly reduced (p< 0.05) after topical treatment with either lomefloxacin or ciprofloxacin. For Gram-positive bacteria, lomefloxacin and ciprofloxacin were equally effective. For Gram-negative bacteria, lomefloxacin, while effective, was less so than ciprofloxacin under experimental conditions (p< 0.05).Conclusion.Our data, using multiple bacterial keratitis models, suggest that lomefloxacin is promising for therapy of bacterial keratitis. Further clinical studies are needed to expand its use for keratitis therapy.