Aim To investigate the effect of recombinant human vascular endothelial growth factor-dextran-polylactic acid-glycolic acid (VEGF-dextran-PLGA) sustained-release microspheres on promoting angiogenesis in ischemic lower limbs of rats. Methods VEGF-dextran-PLGA microspheres were prepared and their morphology was observed by scanning electron microscopy. The drug release properties were determined by ELISA in vitro. The fibrin gel loaded with VEGF-dextran-PLGA microspheres was injected into the ischemic lower limb muscle of rats, and histological and immunohistochemical staining were performed 1 month later to evaluate the angiogenesis. Results VEGF-dextran-PLGA microspheres released VEGF in vitro for more than 4 weeks. They could significantly increase the density of capillaries and α-smooth muscle actin-positive blood vessels at the injection site, and promote the mobilization of CD34, C-kit and VEGFR-2 positive cells. Conclusion Intramuscular injection of fibrin gel loaded with VEGF-dextran-PLGA microspheres is an ideal therapeutic angiogenesis method.