LL-37/hCAP-18, a human cathelicidin antimicrobial peptide, plays a key role in angiogenesis. This study demonstrates that LL-37 induces angiogenesis by directly activating endothelial cells through the formyl peptide receptor-like 1 (FPRL1). In vitro and in vivo experiments show that LL-37 promotes neovascularization in the chorioallantoic membrane assay and in a rabbit model of hind-limb ischemia. LL-37 increases endothelial cell proliferation and the formation of vessel-like structures. In mice deficient for CRAMP, the murine homologue of LL-37, wound vascularization is impaired, indicating that cathelicidin-mediated angiogenesis is essential for cutaneous wound healing. LL-37 activates endothelial cells via FPRL1, leading to increased intracellular calcium and NF-κB translocation, which are critical for angiogenesis. The peptide also activates signaling pathways such as PLC, PI3K, and MAPK. These findings highlight the multifunctional role of LL-37 in innate immunity, linking host defense, inflammation, and angiogenesis. LL-37/hCAP-18 may serve as a therapeutic agent for inducing angiogenesis in diseases involving impaired blood supply.LL-37/hCAP-18, a human cathelicidin antimicrobial peptide, plays a key role in angiogenesis. This study demonstrates that LL-37 induces angiogenesis by directly activating endothelial cells through the formyl peptide receptor-like 1 (FPRL1). In vitro and in vivo experiments show that LL-37 promotes neovascularization in the chorioallantoic membrane assay and in a rabbit model of hind-limb ischemia. LL-37 increases endothelial cell proliferation and the formation of vessel-like structures. In mice deficient for CRAMP, the murine homologue of LL-37, wound vascularization is impaired, indicating that cathelicidin-mediated angiogenesis is essential for cutaneous wound healing. LL-37 activates endothelial cells via FPRL1, leading to increased intracellular calcium and NF-κB translocation, which are critical for angiogenesis. The peptide also activates signaling pathways such as PLC, PI3K, and MAPK. These findings highlight the multifunctional role of LL-37 in innate immunity, linking host defense, inflammation, and angiogenesis. LL-37/hCAP-18 may serve as a therapeutic agent for inducing angiogenesis in diseases involving impaired blood supply.