1. In the present study we investigated the effect of spermine diazeniumdiolate (spermine-NONOate), a nitric oxide donor, on the early development of atheroma-like lesions induced by a peri-arterial collar in rabbits. 2. Spermine-NONOate was given locally by incorporating the compound (1 mg/mL) into a silastic collar, which was applied on one common carotid artery of rabbit while the other carotid artery had a placebo collar (without compound) applied. 3. Fourteen days postimplantation, both carotid arteries were dissected free for histological study (n = 6). 4. After 14 days with collars, treatment with spermine-NONOate had significantly reduced (by 74%) the thickness of the neointima in comparison with the contralateral collared artery without compound, Blood pressure did not change during treatment, Nitric oxide, detected as nitrite, was still released from spermine-NONOate silastic collars after 14 days implantation. 5. These results suggest that locally administered spermine-NONOate is effective in slowing the development of neointima in this model.