Objective: To clarify the antioxidation role in diabetic ED treatment by a long-term administration of PDESI.Methods: Three groups of Sprague-Dawley rats were utilized: group N,normal control;group D,streptozotocin(STZ)induced diabetic rats as control;group D + T,STZ induced diabetic rats by the intragastric administration with tadalafil for 8 weeks.Results: ICP/MAP ratio was significantly higher in group D + T than in group D.The levels of MDA decreased remarkably and the activities of SOD increased significantly of group D + T,compared with group D.The level of mitochondrial membrane potential of cavernous tissue of diabetic rats was partly recovered by tadalafil treatment for 8 weeks.The morphology changes of mitochondria were also ameliorated in group D + T.Conclusions: The long-term administration of tadalafil on diabetic rats is proven to partly lessen the oxidative stress lesion of the penis via a local antioxidative stress pathway.Early longterm dosages of tadalafil once daily maybe partly prevent rats from diabetic erectile dysfunction.To our knowledge,this is the first report to reveal the new mechanism on long-term treatment of tadalafil in diabetic ED.