The effect of UF-021, a prostaglandin-related compound which has recently become available for treatment as an antiglaucoma agent, on the circulation of the optic nerve head (ONH) was studied in normal rabbit eyes and in eyes with circulation insufficiency induced by endothelin-1 (ET-1). The capillary blood flow in the ONH was measured for 5 hours using a hydrogen gas clearance flowmeter, and the intraocular pressure (IOP) was also measured. A single instillation of UF-021 reduced the IOP (maximum reduction: 3.7 mmHg at 2 hours) but had no effect on ONH blood flow in normal rabbit eyes. Intravitreal injection of UF-021 reduced IOP to a lesser extent (maximum reduction: 1.8 mmHg at 3.5 hours) and significantly increased ONH blood flow from 1 to 3.5 hours (maximum increment: 14% of the initial value at 1 hour). Pretreatment with intravitreal injection of UF-021 did not affect IOP but partly inhibited the ONH blood-flow-decreasing effect of ET-1. These results suggest that UF-021 can improve ONH probably by reducing the resistance in ONH blood vessels.