Objective: Erectile dysfunction(ED)is one of the most common complications of diabetes mellitus(DM).Under the background that effectivity of treatments for diabetic ED are quite poor,stem cell therapy is emerging a useful method.The aim of this study is to evaluate the possibility and mechanism of treatment of diabetic ED with endothelial progenitor cells(EPCs)genetically modified by human telomerase reverse transcriptase(hTERT).Methods: Rat EPCs were isolated and transfected with hTERT(EPCs-hTERT).The paracrine characters and resistance to oxidative stress of EPCs-hTERT was determined in vitro.Thirty SD male rats were divided into five groups: diabetic ED rats,diabetic ED rats treated with EPCs,diabetic ED rats treated with EPCs-control,diabetic ED rats treated with EPCs-hTERT,normal control rats.Diabetes was induced by intraperitoneal injection of streptozotocin.After 8 weeks,diabetic ED rats were selected by apomorphine(APO)test.After injection of EPCs for 2 weeks,intracavernosal pressure(ICP)was measured by means of electrical stimulation for each group.Concentration of growth factors,the amount of EPCs and endothelium/smooth muscle content were evaluated in vivo.Results: EPCs-hTERT showed stable expression of hTERT at the level of,mRNA and protein for more than 40 passages.EPCs-hTERT could paracrine more VEGF,HGF and bFGF.EPCs ability of resistance to oxidative stress was dramatically improved by tranfection of hTERT.ICP/mean arterial pressure(MAP)ratio induced by electrical stimulation in diabetic ED treated with EPCs-hTERT was markably higher than diabetic ED rats treated with EPCs or EPCs-control.Immunofluorescence demonstrated that more cells survived in penile tissues after implantation of EPC-hTERT.More growth factors were detected,and the endothelium/smooth muscle content was increase in penile tissues.Conclusions: The paracrine effect and resistance to oxidative stress of EPCs-hTERT contributed to the improvement of erection of diabetic ED rats.