Copper (Cu)-bearing stainless steel with release of Cu2+ ions is a novel material for coronary stents that could reduce the in-stent restenosis after the stent implantation. The inflammation has been recently recognized as an important factor to smooth muscle cells proliferation, thrombosis, and hence the restenosis post-angioplasty. The objective of this study is to further investigate the effect and relevant mechanism of Cu-bearing stainless steel (316L-Cu SS) on the inflammation reaction after stent implantation. The results demonstrated that, compared with commercial coronary stent material (316L SS), 316L-Cu SS could inhibit the inflammation caused by endothelial dysfunction through blockading the inflammatory factors (TNF-α, IL-1β, 6, 8), which would then reduce the recruitment and infiltration of leukocytes, rather than have direct effect on leukocytes. This finding further explained the reduction effect of 316L-Cu SS on in-stent restenosis from a novel view.