Ischemic stroke was a leading cause of death and long-term disability. It was an effective way to improve cerebral ischemia injury by promoting angiogenesis and neuroprotection. Vascular endothelial growth factor (VEGF) was a potent pro-angiogenic factor, and had neuroprotective effect. A short peptide (PR1P) derived from the extracellular VEGF-binding glycoprotein-Prominin-1 was reported to specifically bind to VEGF. In order to realize sustained release of VEGF, a bio-functional peptide-CBD-PR1P was constructed, which target VEGF to collagen hydrogels to limit the diffusion of VEGF. When the collagen hydrogels loading with CBD-PR1P and VEGF were injected into the cerebral ischemic cortex, increased angiogenesis, decreased apoptosis and enhanced neurons survival were observed in the ischemic area, that promoted the motor functional recovery of cerebral ischemic injury. Thus, this targeting delivery system of VEGF provided a promising therapeutic strategy for cerebral ischemia.