PURPOSE: To determine the effect of azithromycin (AZM) in a murine model of corneal inflammation. METHODS: The effect of topical AZM was studied in murine corneal inflammation. Corneal inflammation was induced by thermal cautery in BALB/c mice. Leukocyte infiltration at different time points was analyzed by flow cytometry. At set time points, real-time polymerase chain reaction was performed to quantify the expression of different inflammatory cytokine transcript in the cornea. Corneal samples were analyzed immunohistochemically for the expression of intercellular adhesion molecule-1 (ICAM-1). Corneal neovascularization (CNV) was induced by micropellet (VEGF-A) placement. Mice were then treated topically with either AZM or vehicle. CNV was evaluated morphometrically. RESULTS: Eyes receiving AZM showed a significant decrease in corneal infiltration compared with the vehicle-treated group. AZM also significantly decreased messenger RNA expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and ICAM-1 in the cornea. There was no significant difference in CNV between the AZM- and vehicle-treated groups. CONCLUSIONS: After an inflammatory insult, topical AZM significantly reduced leukocyte infiltration into the cornea. This was further supported by an associated decrease in expression of IL-1β, TNF-α, and ICAM-1 in the cornea, indicating AZM may have a potential anti-inflammatory effect on corneal inflammation.