Background We investigated the mechanism of in-stent restenosis in radius stents in comparison to balloon-expandable stent (NIR stent) in pigs, with a focus on extracellular matrix (ECM). Methods and Results Radius (n=4) or NIR (n=4) stents were implanted in the left coronary arteries of miniature pigs. Quantitative coronary ultrasound (QCU) was performed before, immediately after, and at 1 and 4 weeks after the implantation. The stented-coronary arteries were harvested at 4 weeks after the implantation followed by immunohistochemical, histological, reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR studies. In QCU, mean luminal areas at 4 weeks did not differ between both groups, whereas the mean stent area and neointimal area were significantly greater in the radius (p<0.01). The immunohistochemical study revealed a significantly decreased number of neointimal macrophages and neovascularizations (p<0.05, p<0.01, respectively), and a stronger expression of tenascin-C in the radius. The histological study showed a larger ECM area and less neointimal cell density in the radius than in the NIR. The RT-PCR and real-time PCR analysis revealed an enhanced expression of tanascin-C mRNA in the radius than in the NIR. Conclusions Increased production of ECM, especially tenascin-C, played a greater role in the neointimal formation in the radius stent than inflammation. (Circ J 2005; 69: 481 - 487)