Restenosis is the major clinical problem of angioplasty. We have previously shown that neointima formation is strikingly suppressed in midkine-deficient mice. Neointima formation is restored if midkine protein is administrated to the deficient mice. Midkine is a heparin-binding growth factor, and implicated in the migration of inflammatory cells and vascular smooth muscle cells. Consistently, the suppression of neointima formation in the deficient mice is accompanied by suppression of recruitment of inflammatory cells into the vascular wall. Here, we evaluated the potential of MK antisense oligodeoxyribonucleotide (ODN) for the prevention of restenosis. We cloned the cDNA of rabbit midkine, which showed a strongly conserved sequence in mammals. The balloon injury induced midkine expression, the maximum level occurring 7-14 days after angioplasty, in the rabbit carotid artery. Two antisense ODNs suppressed the production of midkine in a rabbit kidney cell line, RK13 cells, one of which was then transfected into the arterial wall by means of lipofection immediately after balloon treatment. The antisense ODN suppressed midkine induction in vivo, and consequently suppressed neointima formation to 60% of the control level. These results suggest that midkine is a candidate molecular target for the therapy for vascular restenosis.