We compared the ocular tissue and systemic blood distribution patterns of clonidine, an alpha 2-adrenergic agonist with ocular hypotensive activity, after topical application with ophthalmic rods or ophthalmic solution (eyedrops) in rabbits. We measured tissue concentrations at 0-240 minutes after administration with rods containing 5 micrograms, 10 micrograms, or 20 micrograms clonidine, or a 0.125% (62.5 micrograms) solution. The delivery efficiency of the rods was 65 - 71%. The rods and eyedrops had similar absorption and distribution patterns intraocularly and in systemic blood. Tissue concentrations of clonidine achieved were proportional to the dose delivered; peak ocular tissue concentrations were reached within 20 minutes (except for the lens). Clonidine concentrations were: tears greater than cornea greater than iris/ciliary body greater than or equal to aqueous humor greater than lens. We concluded that the ophthalmic rod offers a viable alternative to ophthalmic solution for the topical delivery of clonidine.