Background Coronary artery in-stent restenosis (ISR) and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin (IL)-1β.Methods Mini pigs (n=12; 2-3 months old and weighing 25-30 kg) were subjected to thoracotomy. Segments (10 mm)of the mid left anterior descending coronary artery and left circumflex coronary artery were exposed and aseptically wrapped with a cotton mesh soaked with IL-1β (5 μg). After 2 weeks, the animals were anesthetized and quantitative coronary arteriography (QCA) was performed. The stenosis sites were randomized into three groups for stent insertion: a sirolimus-eluting stent (SES) group (FirebirdTM, n=7), a paclitaxel-eluting stent (PES) group (TAXUSTM, n=9), and a bare-metal stent (BMS) group (YINYITM, Dalian Yinyi Biomaterials Development Co., Ltd, China, n=8). The three different stents were randomly implanted into stenosis segments. Expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), P-selectin and vascular cell adhesion molecule-1 (VCAM-1) was determined by reverse transcription-coupled polymerase chain reaction (RT-PCR).Results QCA showed severe stenosis in IL-1β treated segments. The SES and PES groups showed lower 1-month angiographic late lumen loss (LLL) within the stent and the lesion compared with BMS (P ＜0.05) by follow-up QCA. The SES showed lower LLL than that of PES in reducing 1-month inflammation lesions in pigs by follow-up QCA ((0.15±0.06)mm vs. (0.33±0.01) mm, P ＜0.0001). The neointimal hyperplasia areas in SES and PES showed lower than those of BMS (SES (11.6±1.7) mm2, PES (27.2±1.6) mm2 vs. BMS (76.2±1.3) mm2, P ＜0.0001). The mRNA expression of MCP-1 by RT-PCR in SES and PES showed lower than that of BMS at 30 days after stenting (SES 0.20±0.03, PES 0.48±0.49 vs.BMS 0.58±0.07, P ＜0.05). Levels of VCAM-1 in SES were significantly lower than those of PES and BMS (SES 0.35±0.08 vs. PES 0.65±0.13, BMS 0.70±0.06, P ＜0.05). Histochemical immunostaining of vessel walls showed lower inflammatory chemokine MCP-1 expression in the SES and PES groups compared with BMS.Conclusion SESs were superior in reducing 1-month angiographic LLL in inflammation lesions in pigs, strongly suggesting that SESs can suppress inflammatory reactions in ISR at multiple points.