INTRODUCTION: Soft tissue defects in Maxillofacial region remain significant health problems. The correct architecture and function of the vastly diverse tissues of this important anatomical region is mandatory. Amniotic membrane (AM) has been recently proposed as costeffective alternative skin graft. It provides significant benefits by improving the process of wound healing and minimizing scar formation. OBJECTIVES The aim of the present study was to assess clinically and histologically the effect of the use of the human amniotic membrane in healing of surgically induced skin defects in rabbits. MATERIALS AND METHODS: This study was performed on 14 White New Zealand rabbits on which skin defects were created on both sides of their back. The right side was grafted with human amniotic membrane (AM) freshly obtained and cryopreserved (side A), and the left side was left to heal spontaneously by secondary intention (side B). The rabbits were divided later in to three groups according to intervals of evaluation and sacrification (1st week, 2nd and 3rd week postoperative). The wounds were examined for gross morphological evaluation, histological and immunohistochemical studies. RESULTS Percentage of wound closure in AM grafted wounds was significantly higher than control wounds at 1st and 2nd week, but not significant at 3rd week healing wound (P<0.061). Histologically, the wounds of side (A) showed less inflammatory reaction and thicker newly formed epidermis layer. Collagen fibers were arranged in many directions and had higher density than those found in control wounds. Immunohistochemical evaluation showed higher expression of CD31 in side (A) than side (B) wounds indicating better angiogenesis in AM grafted wounds. CONCLUSIONS: AM graft enhanced and speeded up the healing process and wound closure with less scar healthy tissue.