Background: Cilostazol is a selective inhibitor of phosphodiesterase-3 that increases intracellular cyclic AMP `levels and activates protein kinase A, thereby inhibiting platelet aggregation and inducing peripheral vasodilation. Currently, an increasing number of studies have shown the potent anti-inflammatory actions of cilostazol. Type 1 diabetic patients have an increased risk of in-stent restenosis. Underlying pathogenic mechanisms are not fully understood due to the lack of a relevant animal model. In the present study, we evaluated the effects of cilostazol in in-stent restenosis, thrombus, and inflammation reaction in a diabetic rat model. Methods: Type I diabetic rat model was manipulated by intra-peritoneal streptozotocin injection and normal control rats received an injection of buffer alone. Two groups were divided into another two groups by cilostazol oral treatment or not. All of four groups (n=4 in each) underwent paclitaxel-eluting stent implantation in aorta. Four weeks later, stented aorta was isolated and histomorphometric analysis was performed. Results: In vitro assay using rat vascular smooth muscle cells, cilostazol attenuated the vascular cell adhesion molecule-1 expression induced by TNF-alpha (10 ng/ml) in high glucose condition. The similar pattern was also observed in the human umbilical endothelial cells. According to the scanning electron microscopic finding, a possible acute thrombus lesion with abundant red blood cells deposit covered with thin fibrin structure at the stented aorta in diabetic rats and cilostazol treatment decreased this thrombus in diabetic rats. Histomorphometric analysis demonstrated that cilostazol treatment induced more re-endothelialization at the stented aorta and preservation of endothelial cell layer at the non-stented aorta. Conclusions: In conclusion, cilostazol had a protective effect on endothelial cells in diabetic rats with paclitaxel-eluting stent. And cilostazol can be applied in diabetic patients who underwent drug-eluting stent implantation via anti-thrombotic and anti-inflammatory therapeutic potentials.