This study examined whether borneol could enhance corneal drug permeability. Model drugs containing either synthetic or natural borneol were co-administered to isolated intact or de-epithelialized rabbit corneas and the apparent permeability coefficients were measured. Draize tests in rabbits and levels of isolated intact rabbit corneal hydration were used to measure in vivo and in vitro toxicity, respectively. Synthetic borneol (0.1%) increased corneal penetration of the lipophilic agents, indomethacin and dexamethasone, by 1.23 and 2.40, respectively, and of the hydrophilic agents, ofloxacin, ribavirin and tobramycin, by 1.87, 2.80 and 3.89, respectively. For natural borneol, the corresponding fold increases were 1.67, 2.00, 2.15, 2.18 and 3.39, respectively. Removing the epithelium attenuated the penetration-enhancing effects of borneol. Borneol (0.1%) did not damage corneal tissue. The ability of borneol to enhance drug penetration through the outer corneal layer, particularly for highlyhydrophilic drugs, suggests that further clinical investigation may be warranted.