Corneae of guinea pigs were burned with 200 μl IN-NaOH for 30 seconds. Topical application of 1%, 0.1%, or 0.025% indomethacin (IN) four times daily resulted in a marked delay of corneal re-epithelialization compared to corneae receiving the vehicle only. However, no retardation of corneal wound healing was observed when IN was injected intraperitoneally (5 mg/kg) twice daily, but hyperemia and chemosis were reduced.To study the proportion of retained IN in burned cornea, 0.1% IN was mixed with a tracer dose of [2-14C] IN: 3.4, 1.2, 0.42, and 0.24% of the dose were retained 20, 60, 180, and 360 minutes respectively after topical application of 15 μl. Twenty minutes after application of 15 μl 0.1% IN, the concentration of retained IN in thecorneawas 31 μg/g, which is considerably higher than the average concentration of 0.358 μg/ml1found in human blood plasma after therapeutic doses of IN.Thus, the retardation of corneal wound healing may be explained by a cytotoxic effect of supratherapeutic concentrations of IN.