Despite advanced techniques of stent placement which cause fewer traumas to the vessel walls; as well as introduction of drug-eluting stents which result in the least induction of immune response, in-stent restenosis (ISR) is still one of the common and severe complications after PCI and stent placement. Intimal hyperplasia following immuno- inflammatory response of the arterial wall to balloon injury has been proposed as main mechanism of ISR. In a prospective study, we assessed the predictive role of Interleukin (IL)-18 and tumor necrosis factor alpha (TNF- α) as pro-inflammatory cytokines and IL-10 as anti-inflammatory cytokine and high sensitive C-reactive protein (hs- CRP) for ISR. 128 patients (mean age=59±10.2, female/male: 41/87)who underwent percutaneous coronary intervention (PCI) and stent implantation. Venous blood samples were obtained before and 24 hours after PCI. IL- 18, IL-10, TNF-αand hs-CRP levels were determined. We followed the patients for24months and measured the incidence of ISR via angiography. Results were compared between ISR and non-ISR patients. 20 patients (15.6%) developed ISR. Serum level of IL-18, TNF-α and hs-CRP have been increased in all patients 24 hours after PCI. Serum level of IL-18 at 24-hours was not different between ISR and non-ISR patients (p=0.239), while serum level of IL-10 was significantly higher in non-ISR group (p<0.001). IL-18/IL-10 was significantly higher in ISR patients than in non-ISR patients (p<0.001). IL-18/IL-10 can be applied as predictive factors for ISR.