Recent studies have demonstrated the existence of a population of adipose tissue-derived adult stem cells that can undergo multilineage differentiation in vitro; however, it is unclear whether these cells maintain their multilineage differentiation in vivo. The objective of the present study was to examine the in vivo characteristics and behavior of a potential population of human adipose tissue-derived adult stem cells. Herein, we demonstrate that human adipose tissue-derived adult stem cells differentiate into the epithelium of the gastrointestinal tract, liver, and bronchi, and an endothelial lineage after transplantation into irradiated nonobese mice with diabetes or severe combined immunodeficiency. These findings may contribute to clinical tissue repair after injury.