S100A9 is a pro-inflammatory protein expressed in infiltrating granulocytes and monocytes. We determined role of S100A9 in endotoxin (LPS)-induced uveitis (EIU) and keratitis in Wistar rats. Anti-S100A9 antibody decreased partially clinical scores, protein, and cells in the aqueous humor at 18-36 h, compared with the LPS group. S100A9-positive cells were expressed in the iris-ciliary body (ICB) and cornea at 24-48 h. Activated caspase-3 (related to apoptosis) and S100A9 co-expressed in ICB at 18-48 h after LPS injection. S100A9 was not expressed in ED2-positive cells in ICB. Dexamethasone (DEX) increased S100A9 mRNA and protein levels in the circulating blood leukocytes, but reduced S100A9 mRNA and protein levels in ICB after LPS injection. BAY 11-7085 (an inhibitor of I-kappaB phosphorylation) suppressed S100A9 mRNA in leukocytes (43.5%) and ICB (68.5%), respectively, after LPS injection. It is possible that S100A9-positive granulocytes and monocyte/macrophages may play a role in the late phase of EIU and keratitis that DEX may inhibit the migration of S100A9-positive granulocytes and monocytes from the blood into the extravascular tissues, and that nuclear factor (NF)-kappaB pathway may be involved in S100A9 expression. S100A9 could play a role in the clearance of inflammatory cells at the late phase of EIU.