Cultured epidermal sheets are currently used for burn wound treatment but reported results on graft take are variable. This study was designed to evaluate the role and influence of Tisseel, a fibrin glue, in the take of cultured human epidermal sheets in an athymic mouse model. On days 4, 10 and 21 post-grafting, histology, electron microscopy and immunofluorescence staining confirmed the presence of a human epithelium and the development of a basement membrane. Tisseel was detectable on day 4 only, but overall treated and untreated grafts were similar. The use of Tisseel enhanced the mechanical stability of these fragile grafts, increased the percentage of graft take, and its innocuity on the in vivo evolution of cultured epidermal sheets was demonstrated. For these reasons, we think that Tisseel may be advantageous in a clinical setting.