Background: Current evidence suggests that human adipose tissue-derived stem cells (hADSCs) hold promise for cardiovascular regenerative therapy. Objective: The aim of this study was to investigate the pluripotency of hADSCs in vivo and the long-term ability of hADSCs to improve cardiac function and left ventricle remodeling in the severe combined immunodeficiency NOD.CB17-Prkdc scid/J mice (NOD/SCID) model with acute myocardial infarction (AMI). Materials and methods: Total 50 NOD/SCID mice, 12 weeks old, were randomized into three groups, namely, AMI+media (control), AMI+hADSCs and AMI+transgenic-hADSCs. AMI was produced by left anterior descending coronary artery ligation. After AMI induction, 1��106 hADSCs and transgenic-hADSCs or media only were intramyocardially injected. 2-D echocardiography for cardiac function test and histological analyses were performed at 4 weeks in 28 mice out of 50 mice and 8 weeks in 22 mice out of 50 mice after AMI. Results: Left ventricle ejection fraction was improved between two cells therapeutic groups compared with control group at 4 and 8 weeks after AMI (p = 0.000 and 0.002, respectively). Left ventricle dimension was decreased significantly in the cells-implanted groups versus control group at 4 weeks after AMI (p = 0.015 and 0.000, respectively) but there were no statistical differences among three groups at 8 weeks after AMI. We observed that hADCSs migrated into injured sites and the vascular density in the infarct border zone also was improved in the two cells-grafted groups compared with control group. Additionally, the grafted hADSCs co-localized with endothelial marker, von Willebrand factor, and incorporated into newly formed vessels, however, did not co-localized with cardiac muscle marker such as troponin I and connexin 43 at 4 and 8 weeks after AMI. Conclusions: These results indicate that transplantation of hADSCs could improve cardiac function via angiogenesis. However, whether hADSCs have a potential to differentiate into cardiomyocyte in vivo is not shown clearly.