Abstract: Objective To investigate the effects of vascular endothelial growth factor (VEGF) gene transfection on survival of the random skin flap in rats. Method Thirty SD rats were randomized equally into 3 groups: pcDNA₃-VEGF₁₆₅, pcDNA₃ and control groups, with the former two groups transfected via liposome with pcDNA₃-VEGF₁₆₅ and pcDNA₃ respectively 48 h before and during the operation. Isehemic random skin flaps (1 cm×7 cm) were constructed from the rats. Seven days later, the amount of viable tissue within the flap was measured by planimetry. After the animals were killed, and specimens from the random skin flaps were harvested for immunohistologic evidence of VEGF protein expression and for HE staining to examine the microvascular growth. Results The results of tissue survival planimetry of the skin flap of pcDNA₃-VEGF₁₆₅, pcDNA₃ and control groups were 48.46%±3.35%, 30.20%±2.16%, and 31.35%±1.99%, which were highest in the VEGF- transfected group (P<0.05), in which immunohistochemical staining revealed increased deposition of VEGF in comparison with the other control groups (P<0.05). The VEGF group had also higher average vessel number as compared with the vector and control group (107.72±9.42 vs 91.35±7.28 and 89.85±7.66, P<0.05), and smaller average vessel lumen diameter (25.76±3.23 μm vs 32.12±1.58 μm and 33.49±2.29 μm, P<0.05). Conclusion pcDNA₃-VEGF₁₆₅ transfection may enhance the survival of the ischemic skin flaps and achieve VEGF expression in the flaps in rats.