Grafting of cultured epidermal sheets is a promising technique for skin restoration in extensive burns, but the technique has some limitations, resulting in variable graft takes. These experiments were designed to evaluate the innocuity of Hemaseel HMN fibrin sealant in the grafting process and in vivo evolution of cultured epidermis. A total of 30 mice were grafted, 15 were controls, 15 received tissue sealant application before the deposition of the cultured human epidermal sheets. Seven days after transplantation, compared to controls, the percentage of graft take over the total surface area grafted was greater in animals that had received the tissue sealant application. No difference was found 14 and 21 days postgrafting. In contrast, the percentage of graft take over the bony area (spinal) was significantly increased in animals grafted with previous application of sealant compared to controls at 7, 14 and 21 days postgrafting. Immunohistological and ultrastructural analysis showed that the evolution of the cultured human epidermis after transplantation was similar in both groups. The basement membrane was well structured 21 days after transplantation. The sealant was present at 4 days but not at 21 days postgrafting. Therefore, we conclude that the application of fibrin sealant before cultured epidermal sheet deposition on nude mouse graft bed is innocuous and enhances their mechanical stability. Since in this nude mouse system Hemaseel HMN fibrin sealant increased the percentage of graft take over areas difficult to engraft, we think that it may be advantageous in cultured epidermal sheet grafting on burn patients.