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In this study, the effects of ginsenoside Rg₁, a natural compound isolated from Panax ginseng, on human umbilical vein endothelial cell (HUVEC) behavior in vitro, and on angiogenesis and tissue regeneration in genipin-fixed acellular tissue (extracellular matrix, ECM) in vivo, were investigated. Basic fibroblast growth factor (bFGF) was used as a control. The in vitro results indicated that in the presence of bFGF or Rg₁, HUVEC proliferation was significantly increased. Both bFGF and Rg₁ promoted HUVEC migration in a Transwell plate assay. In addition, bFGF or Rg₁ significantly increased the formation of capillary-like network by HUVECs on Matrigel. Thus, both bFGF and Rg₁ enhanced multiple components of angiogenic activity in vitro. The in vivo results obtained 1 week postoperatively showed that the extent of angiogenesis in ECMs was significantly enhanced by bFGF or Rg₁. At 1 month postoperatively, vascularized neoconnective tissues were found to fill the pores within ECMs loaded with bFGF or Rg₁. There was a significant increase in neocapillary density from 1 week to 1 month for ECMs loaded with Rg₁, whereas that observed in ECMs loaded with bFGF stayed approximately the same because of the limitations of protein stability. These results suggested that Rg₁ may be a new class of angiogenic agent and may be loaded in ECMs to accelerate tissue regeneration.