The present study was designed to investigate the possible effect of vardenafil phosphodiesterase-5 inhibitor on diabetic foot ulcer induced in rats and the underlying mechanism(s).Streptozotocin -induced diabetic rats were treated with the phosphodiesterase-5 inhibitor, vardenafil, for 8 weeks starting on day 15 after Streptozotocin injection. After 4 weeks of treatment, a wound of fixed size was induced in the dorsal surface of right foot and wound size measured every 3 days. Behavior tests (foot print and hotplate test) were performed every 2 weeks. At the end of the study, animals were euthanized, body weight, serum insulin, glucose, glycated haemoglobin, interlukin-6, adiponectin and hematoxylin and eosin stained sections were investigated.Diabetes resulted in delayed wound healing, elevated blood glucose, HbA1c, IL-6, reduced serum insulin and adiponectin, treatment with vardenafil lead to improvement in all tested parameters.In conclusion, the phosphodiesterase 5 inhibitor vardenafil can be used for the treatment of diabetic foot ulcer (DFU) since it is already used for other indications. Further studies are required to confirm its effects either alone or combined with other antidiabetic therapies.