Alkali　burn　is　a　significant　contributor　to　corneal　injury.　Alkali　burn-induced　corneal　inflammation　often　causes　vision　loss　due　to　corneal　neovascularization.　Daphnetin　(DAP)　has　been　studied　for　its　anti-inflammatory　and　antiangiogenic　properties　with　encouraging　results.　Driven　by　those　encouraging　results,　we　sought　to　explore　the　effects　of　DAP　in　treating　alkali　burn-induced　corneal　inflammation　and　neovascularization　and　its　mechanism　of　action.　We　found　that　the　angiogenesis　processes　of　human　umbilical　vein　endothelial　cells　(HUVECs)　induced　by　vascular　endothelial　growth　factor　A　(VEGF-A)　were　primarily　attenuated　by　treatment　with　DAP,　including　proliferation,　migration,　and　tube　formation.　Treatment　of　DAP　significantly　suppressed　the　VEGF-Ainduced　protein　expression　of　VEGF　receptor2　(VEGFR2),　as　well　as　the　activation　of　downstream　signal　transducer　and　activator　of　transcription　3　(STAT3),　AKT,　and　extracellular　signal-regulated　kinase　(ERK)　signaling.　In　the　mouse　corneal　alkali　burn　model,　the　inflammatory　cell　infiltrations　and　neovascularization　in　the　cornea　caused　by　alkali　burn　were　inhibited　by　10　mu　M　DAP　eye　drops.　Alkali　burn-induced　corneal　protein　expression　of　VEGF-A,　VEGFR2,　phosphorylated　(p-)STAT3,　p-AKT,　and　p-ERK　in　corneal　tissue　were　reduced　mainly　by　DAP.　Moreover,　the　upregulation　of　inflammatory　caused　by　alkali　burn　in　the　pathological　process　was　significantly　neutralized　by　DAP.　Mechanistically,　the　inflammatory　response　could　be　alleviated　by　DAP　in　the　way　of　inhibiting　the　expression　levels　of　TLR4,　p-NF-kappa　B,　NLRP3,　ASC,　Cleaved-caspase-1　(p20),　mature-IL-113　(p17),　and　N-GSDM.　In　conclusion,　our　findings　confirmed　that　the　corneal　inflammation　and　neovascularization　caused　by　alkali　burn　could　be　inhibited　by　DAP　in　vitro　and　in　vivo,　elucidating　the　underlying　mechanisms　of　its　protective　effects.　DAP　may　have　tremendous　therapeutic　potential　for　the　treatment　of　corneal　alkali　burn.