The objective of this study was to assess the in vitro release kinetics and the in vivo angiogenic effect of human vascular endothelial growth factor (VEGF)-activated poly(DL-lactide-co-glycolide) (PLGA) sponge. The highly porous sponges (each 3 x 4 x 4 mm(3)) were activated by soaking in a VEGF solution (2.5 or 5.0 microg) and then freeze-drying. In vitro release in PBS was investigated by a competitive enzyme immunoassay for up to 3 weeks. The burst-type initial release within the first 3 days followed a more controlled one lasting for >2 weeks. The angiogenic potential of the VEGF sponge was evaluated by subcutaneous implantation into the epigastric groin fascia of Wistar rats. Histomorphometry and SEM confirmed the formation of new capillaries infiltrating the sponge pores starting from the first week and the drastic anostomosis at weeks 2 and 3. However, the rats implanted with control sponges or receiving VEGF injection exhibited much lower or no angiogenic response, respectively. TEM revealed the neo-vessels had a single endothelial layer surrounded by the matrix inoculated with the rat circulation. The results indicate that VEGF-activated PLGA sponge can be considered as a tool to establish neovascularized subcutaneous transplantation sites for tissue-engineering applications.