Targeted delivery of small extracellular vesicles (sEVs) with low immunogenicity and fewer undesirable side effects are needed for spinal cord injury (SCI) therapy. Here, we show that RGD (Arg-Gly-Asp) peptide-decorated CD163⁺ macrophage-derived sEVs can deliver TGF-β to the neovascular endothelial cells of the injured site and improve neurological function after SCI. CD163⁺ macrophages are M2 macrophages that express TGF-β and are reported to promote angiogenesis and vascular stabilization in various diseases. Enriched TGF-β EVs were crucial in angiogenesis and tissue repair. However, TGF-β also boosts the formation of fibrous or glial scars, detrimental to neurological recovery. Our results found RGD-modified CD163⁺ sEVs accumulated in the injured region and were taken up by neovascular endothelial cells. Furthermore, RGD-CD163⁺ sEVs promoted vascular regeneration and stabilization in vitro and in vivo, resulting in substantial functional recovery post-SCI. These data suggest that RGD-CD163⁺ sEVs may be a potential strategy for treating SCI.