Objectives; Stem cell-mediated gene delivery has considering potential in the cellular cardiomyoplasty. We investigated the efficiency of human adipose tissue-derived stem cell (hADSC) as a gene-delivered vehicle, and the feasibility of EPO gene therapy using hADSC infected lentivirus (hADSC/Lenti-EPO) in a rat model of reperfused ischemic (I/R) heart. Methods; Lentiviral vectors containing the rat EPO gene were made by cotransfection of 293T cell with pRRL-cPPT-CMV-EPO-PRE-SIN, pMDL, pVSVG, and pREV plasmid. In vitro, we identified the GFP expression in hADSC/Lenti-GFP and measured EPO level at the media of hADSC/Lenti-EPO. In vivo, Sprague Dawley rats (n=6, 8 weeks of age) were given I/R injury, induced by ligation of left coronary artery and by reperfusion 5 hours later. DAPI-labeled hADSC/Lenti-GFP or hADSC/Lenti-EPO (1x10⁶ cells, 1x10³ IU, n=3 respectively) were injected at hind-limb on immediate reperfusion. Echocardiographic, histological and Western blot analyses were evaluated after 4 weeks. Results; In vitro, the GFP expression of hADSC/Lenti-GFP was similar with that of HeLa. EPO level in the media of hADSC/Lenti-EPO was higher than hADSC/Lenti-GFP (48 hours after infection; 2283 vs 61 ng/mL). In vivo, blood EPO level in hADSC/Lenti-EPO was increased till 4 weeks (186.0 vs 48.3 mU/mL). All rats treated with hADSC/Lenti-GFP or EPO were survived without any complications. LV systolic function was preserved without dilation in hADSC/Lenti-EPO compared to hADSC/Lenti-GFP (fractional shortening; 33.5짹5.4 vs 14.2짹5.0 %, LV end-diastolic/systolic dimension; 8.4짹0.5/5.6짹0.8 vs 9.2짹0.4/7.6짹0.8 mm). And the fibrosis was decreased. The expressions of EPO���s receptor, PI3K, p-Akt, p-GSK-3��, p-ERK and Bcl-2/Bax were enhanced at hADSC/Lenti-EPO by Western blot analysis. The expression of Caspase-3, the final executor of apoptosis, was decreased. Conclusion; hADSC is efficient cell source as a gene-delivered vehicle, and lenti-EPO gene therapy using hADSC is also safe and feasible. These findings suggest that hADSC-mediated lenti-EPO gene therapy has considering potential for myocardial ischemic protection.