Objectives Many diabetic patients develop foot ulcer that might affect gait, quality of life and may lead to amputation. The present study was designed to investigate the possible effect of phosphodiesterase inhibitors (sildenafil 10 mg/kg/day and vinpocetine 5 mg/kg/day) on healing of experimentally-induced diabetic foot wound in comparison to glimepiride (0.5 mg/Kg/day). Methods All treatments were started on day 15 after streptozotocin (STZ) injection and continued daily for 8 weeks. After 4 weeks of treatment, a wound of fixed size was induced in the dorsal surface of right foot and wound healing was followed throughout the study. Behavior tests (foot print and hot plate test) were performed every 2 weeks. At the end of the study, animals were euthanized, serum insulin, glucose, HbA1C, IL6 and adiponectin were quantified and H& E stained sections (from right foot) were investigated. Results Diabetes delayed wound healing, elevated blood glucose, HbA1c, IL-6, reduced serum insulin and adiponectin. While, treatment with sildenafil, vinpocetine and glimepiride ameliorated most of these effects. Conclusions In conclusion, phosphodiesterase inhibitors as sildenafil, and vinpocetine were effective in ameliorating some of the deleterious effects on diabetes on wound healing indicating that they could be used with other standard therapies for the management of diabetic foot ulcer (DFU).