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Rapid tissue expansion has been attempted, aiming at shortening the period of conventional expansion. However, it has scarcely been clinically applied because of its drawbacks such as low expansion efficiency and tissue destruction. Adipose-derived stem cell transplantation is a promising therapeutic method in regenerative medicine. However, its effects on rapid expansion remain poorly understood.Twenty-four expanders were implanted in the dorsum of 12 pigs. Rapid expansion persisted for 1 week with 20 ml of saline daily. The increased area of the expanded skin was measured. Histologic and ultrastructural analysis and cell tracking were performed. The expression of vascular endothelial growth factor, fibroblast growth factor-2, and epidermal growth factor was also determined.The increased area of adipose-derived stem cell–grafted expanded skin (0.91 ± 0.06 cm2) was significantly more than the non–adipose-derived stem cell–treated control (0.51 ± 0.05 cm2) (p < 0.01). Enhanced tissue regeneration in the adipose-derived stem cell–grafted expanded skin was evidenced by increased skin thickness, proliferating cells, extracellular matrix, and vascularization (113 ± 19/mm2 versus control 59 ± 14/mm2) (all p < 0.05). Higher expression of vascular endothelial growth factor and epidermal growth factor was observed in the adipose-derived stem cell–transplanted expanded skin (p < 0.01 and p < 0.05, respectively), whereas the expression of fibroblast growth factor-2 was higher in the non–adipose-derived stem cell–treated control (p < 0.05). Transmission electron microscopy showed that a high density of collagen fibers could be seen in the adipose-derived stem cell–treated expanded skin. Cell tracking showed that the positively stained cells could be seen.For rapid tissue expansion, adipose-derived stem cell transplantation may limit tissue destruction and improve the expansion efficiency by promoting tissue regeneration.