Innate immune responses in the cornea mainly play an important role to mobilize multiple interrelated pathways of corneal lipid, which involve in inflammatory corneal diseases. Signaling lipid mediators derived from arachidonic acid (AA) control cell proliferation, apoptosis, metabolism, and migration, are known as eicosanoids, phosphoinositides, sphingolipids, and fatty acids. Emerging evidences have highlighted the implication of lipid mediators in both injury and repair mechanisms in the cornea. Recently, the role of AA and its metabolites to induce proinflammatory mediators and inflammatory cell infiltration in the pathogen-infected cornea and to cause severe keratitis have been revealed. In this review, we focus on the novel roles of AA downstream signaling in the corneal inflammatory diseases and also the biological relevance of AA signaling in the therapeutic strategies for targeting sight-threatening diseases.