Abstract.This study examined the ability of nitrova‐sodilator treatment with isosorbide dinitrate to prevent the development of reduced nerve conduction velocity and nutritive blood flow in streptozotocin‐induced diabetes mellitus in rats. Two month untreated diabetes caused approximately 23% and 13% reductions in sciatic motor and saphenous nerve sensory conduction velocity (P<0.001). Isosorbide dinitrate treatment provided 64.6 and 67.6% protection for motor and sensory nerves, respectively (P<0.01). Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and a hydrogen clearance technique. After 1 month untreated diabetes, flow was reduced by 41.9% (P<0.001). Isosorbide dinitrate treatment for 1 month in non‐diabetic and diabetic rats significantly increased blood flow (P<0.01). When between‐group variations in blood pressure were taken into account, vascular conductance increased by 29% and 31% in non‐diabetic and diabetic rats, respectively (P<0.01). Thus, nitrovasodilator treatment improves nerve perfusion and function in experimental diabetes, probably by compensating for reduced endothelium‐derived nitric oxide releas