Vasoactive intestinal peptide is an agonist of VPAC1/VPAC2 receptors (G protein-coupled receptors). In a model of Pseudomonas aeruginosa-induced keratitis, it reduces corneal perforation rates, decreases bacterial load, and inhibits excessive neutrophil infiltration. It enhances anti-inflammatory mediators such as IL-10 and TGF-β while suppressing pro-inflammatory factors like IL-1β and TNF-α, and upregulates lipid mediator-related enzymes (SOCS3, COX-2, ALOX12) to facilitate inflammation resolution. Vasoactive intestinal peptide shows promise for the research of ocular infectious diseases.