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Carbon monoxide-releasing molecules (CORMs) are a novel group of substances that are capable of modulating physiological functions via the liberation of CO.This study was undertaken to investigate the effects of CORM-3, a water-soluble CO-releasing agent, on two rabbit models of ocular hypertension.Ocular hypertension was induced by injecting α-chymotrypsin in the rabbit eye. The dose–response effect of CORM-3 on IOP was assessed by topical administration of the drug (0.001, 0.01, 0.1 and 1%). Ocular hypertension was also obtained by weekly subconjunctival injection of betamethasone, and animals were treated topically with CORM-3. A group of animals in both models was treated with the inactive form of the drug (iCORM-3).CORM-3 induced a dose-dependent reduction in IOP in rabbits treated with α-chymotrypsin. A similar reduction in IOP was observed in rabbits with betamethasone-induced ocular hypertension treated with the drug. Treatment with the iCORM-3 had no effect on IOP in both models.Treatment with CORM-3 is associated with a reduction in IOP in two different rabbit models of ocular hypertension. These results support previous findings on the effect of haem oxygenase-derived CO on IOP and suggest a direct involvement of CO system in the regulation of ocular pressure probably through the modulation of aqueous humour dynamics.