The effect of vascular endothelial growth factor (VEGF) on skin graft survival was studied in rats. Models of skin grafting on muscle and periosteum were designed. For the study of skin grafting on muscle model, 32 rats were divided into 4 groups. VEGF was administrated systemically after skin graft placement intrafascially injected into the recipient bed at the time of graft placement and topically applied to the recipient bed at the time of graft placement. Control groups consisted of grafts placed on sites without systemic or local VEGF treatment. With the study of skin grafting on periosteum, 40 rats were divided into 4 groups. VEGF was systemically, intraperiosteally, and topically applied to the recipient bed. The control animals received no treatment. On the fifth postoperative day, the survival area of each skin graft was measured and the graft was harvested for histology with CD31 immunohistochemical staining. The results showed that in skin grafting on muscle model, the mean viable percentage of the skin graft was 66.1% +/- 10.2% in the group receiving systemic application of VEGF and 56.1% +/- 9.8% in the group receiving VEGF intrafascia injection. The survival percentages were significantly higher than those found in the control group (22.5% +/- 7.7%) and the group with VEGF topical application (30.8% +/- 4.1%). In skin grafting on periosteum, the group receiving VEGF intraperiosteum injection reached a survival percentage of 50.5% +/- 4.3%, significantly higher than the groups with VEGF systemic application (28.7 +/- 5.5%), VEGF topical application (32.5% +/- 4.8%), and the control (25.8% +/- 6.0%). Histology showed that sections taken from grafts with VEGF intrafascia and intraperiosteum treatment revealed angiogenesis. The data demonstrated that administration of VEGF into the either muscular or periosteal recipient beds for skin grafting can improve the skin graft survival.