Oxaliplatin, a platinum-based chemotherapy drug, often induces cumulative sensory peripheral neuropathy. Accumulating evidences suggest a possible relationship between vascular impairment and peripheral neuropathy. In this study, we examined the effects of vasodilators on the oxaliplatin-induced peripheral neuropathy in mice. Mice injected with oxaliplatin (10 mg/kg, i.p.) once a week for 8 weeks showed mechanical (von Frey filament test) and cold (acetone test) hypersensitivities. A single injection of vasodilators (PDE5 inhibitor, endothelin receptor antagonist and prostaglandin analog) 1 h before tests improved the decreased skin blood flow and cold hypersensitivity induced by oxaliplatin, while it had no effect on mechanical hypersensitivity. When mice were fed with diets containing PDE5 inhibitor for 8 weeks during oxaliplatin treatment, the vascular impairment and hypersensitivities to mechanical, cold and transcutaneous current stimuli were suppressed. Furthermore, it prevented the decrease in nerve conduction velocity and axonal degeneration induced by oxaliplatin. These results suggest improvement by PDE5 inhibitor in vascular impairment can prevent oxaliplatin-induced peripheral neuropathy.