At the anastomosis sites after coronary/peripheral bypass grafting for the treatment of atherosclerosis, intimal hyperplasia which induces restenosis or occlusion is commonly followed. In order to prevent such vascular disease with enhanced drug delivery efficiency, we have previously developed perivascular microneedle(MN) devices including MN cuffs and flexible MN meshes. Although the flexible PLGA MN meshes showed significantly improved drug delivery efficiency and efficacy as well as safety to the injured blood vessel, blood vessels were often damaged when relatively stiff PLGA meshes were tightly applied to the blood vessel. Thus, we have developed mechanically adjusted highly stretchable MN meshes using natural biocompatible silk fibroin (SF) protein for localized and secure perivascular drug delivery (Fig. 1). Subsequently, comparative mechanical characterization using rabbit abdominal aorta, PLGA meshes and SF meshes showed significantly soften tensile strength of SF meshes. Finally, we evaluated the efficiency and safety of SF MN meshes for perivascular drug delivery after in vivo animal study.