Sildenafil citrate is a highly selective inhibitor of cyclic guanine monophosphate-specific phosphodiesterase type-5 (PDE-5), leads to smooth muscle relaxation, increases vascular perfusion and tissue blood flow. Clinical and experimental studies previously reported a protective effect of sildenafil in ischemic reperfusion settings in various models. Antioxidants have been reported to reduce ischemia reperfusion injury like vitamin E. Selenium (Se) is one of the most important antioxidants. Antioxidant enzymes such as thioredoxin reductase (TrxR) and glutathione peroxidase along with selenoprotein-P, are responsible for the transport and storage of Se. Nano-elemental Se (SeNPs) are more biocompatible with exhibiting a dramatic decrease in toxicity. Sildenafil and Nano selenium mediated therapeutic angiogenesis in diabetic hind limb ischemia. They improve blood supply, antioxidants delivery for cells and decrease necrosis in peripheral arterial disease (PAD). The induction of therapeutic angiogenesis by sildenafil and SeNPs achieved in this study along with resumed antioxidant defense gives hope of an alternative treatment