Human Acelular Dermis (hADM) and Human de-epidermized dermis (hDED) are collagen type I tissue which suitable for cell attachment, high biocompatibility, and low host immunological rejection. In this study, in vivo study of hADM and hDED were performed. Fresh cadaver skins were harvested, then hADM was prepared by 5 processes, sterilization with glycerol, de-epidermized, fat removal, de-cellularized with enzymatic treatment, and cells residue removal by chemical treatment. hDED was prepared by following 3 processes, sterilization with glycerol, de-epidermized, and fat removal. Both of them were preserved by Freeze-dried method. After that, hADM and hDED were performed histological study, immunohistological study to investigate the architecture of collagen network, and in vivo study to evaluate cell-material interaction. In animal study (n = 18), the specimens were cut into 1x1 cm and were subcutaneous implanted in the back of 3 week-old Wistar rat. 6 rats were sacrificed, and then specimens were collected in each 1, 2 and 4 weeks respectively. The specimens were histological measured by H&E staining and were immunohistochemical investigated the architecture of collagen network by special staining. As a result, neo-vascularization and host tissue fibroblasts infiltration were appeared in hDED more than hADM group. Neo-collagen networks, new extracellular matrix which generated by infiltrated fibroblasts and high ability of cells attachment had been indicated since 1[superscriptst] week in hDED and gradually increased in 2[superscriptnd] and 4[superscriptth] week respectively. In contrast, numerous lymphocytes and foreign body reaction were investigated in hADM. In conclusion, hDED has low foreign body reaction and promote fibroblasts migration and differentiation including recticular network neo-collagen formation. We conclude that remnant fibroblasts which remain in hDED induce foreign body reaction less than losing biological properties of collagen during de-cellularized process of hADM. Biological properties of collagen fiber are important more than complete cell removal by enzymatic or chemical treatment.