The Watanabe heritable hyperlipidemic (WHHL) rabbit produces atherosclerotic lesions (AS) very similar to those in humans and may serve as an animal model for interventional procedures. We used this model to study reparative response after balloon angioplasty at intima-limited vs medial injury sites. Angioplasty was performed on the left subclabian artery of 40 homozygous rabbits, which were sacrificed at 3,7,14,28, or 56 days after procedure. The cellular characteristics of the neointima were studied immunocytochemically, using monoclonal antibodies against smooth muscle actin (actin), macrophage, and vimentin. Finally, the results were compared with our pathological findings of the healing tissues after percutaneous transluminal coronary angioplasty (PTCA) injury in humans. At sites with injuries limited to the atherosclerotic intima, the neointima was mainly composed of macrophages with covering of spindle cells, which showed actin (-) vimentin (+) at day 14 but differentiated into actin (+) smooth muscle cells (SMC) at later stages. At sites with medial injury, however, the neointima predominantly consisted of SMC from day 14 onward. These reparative reactions were almost identical to those observed at intima-limited vs medial injury sites in human coronary arteries after PTCA. These findings in the WHHL rabbit suggest that 1) reparative response after balloon angioplasty in injury limited to atherosclerotic intima differs from that in medial injury, and 2) the WHHL rabbit may serve as a good model for further studies on mechanisms of the response to injury after PTCA in humans.