Background: The cellular and molecular mechanisms, and safety after drug-eluting stents (DES) implantation in diabetic patients are still poorly understood. Therefore, in this study, we evaluated the pathologic responses of the sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES) in type I diabetes mellitus (DM) rat model. Methods: Type I DM rat model was manipulated by intra-peritoneal streptozotocin injection. Two weeks later, DES was implanted in the aorta of rat with hyperglycemia or not as a control. Four weeks after DES implantation, stented aorta was isolated and histomorphometric analysis was performed. Results: At histomorphometric analysis, increased thrombus, inflammatory cells infiltration, and neointimal hyperplasia (NH) without change of smooth muscle cell number after DES implantation were observed in DM rats compared with non-DM rats. Furthermore, delayed a coverage of mature endothelial cells defined as a von willebrand factor expression and increased immature endothelial cells as a c-kit expression after DES implantation were observed in DM rats compared with non-DM rats. Increased fibrin deposition and decreased hyaluronic acid accumulation at NIH after DES implantation were also observed in DM rats compared with non-DM rats. Conclusion: In this study, hyperglycemia with DM rats, restenosis after DES implantation was dependent on initial thrombus with the changes of extra cellular matrix than SMC proliferation. These results provided a therapeutic clue in a selection of DES and application of combination therapy using anti-thrombotic and anti-inflammatory drugs.