PURPOSE. To evaluate the association between iris damage and cytokine levels in the aqueous humor (AqH). METHODS. A total of 201 AqH samples from 201 consecutive patients (mean age 73.7 6 10.6) were collected at the beginning of corneal transplantation or cataract surgery. Iris damage of each case was assessed from preoperative slit-lamp findings based on its severity. The subjects were classified into three groups: eyes without iris damage (126 eyes), eyes with mild iris damage (51 eyes), and eyes with severe iris damage (24 eyes). The levels of cytokines (IL-1a, IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17a, interferon gamma-induced protein [IP]-10, monocyte chemotactic protein [MCP]-1, IFN-alpha, IFN-c, macrophage inflammatory protein [MIP]-1a, MIP-1b, P-selectin, E-selectin, soluble intercellular adhesion molecule [sICAM]-1, TNF-alpha, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in AqH were measured by multiplex beads immunoassay. RESULTS. The levels of aqueous protein, IL-1a, IL-1b, IL-4, IL-6, IL-8, IL-10, IL-17A, MCP-1, TNF-alpha, E-selectin, P-selectin, and sICAM-1 in eyes with mild and severe iris damage were higher than in those without iris damage (P < 0.033). Multivariate analyses of clinical factors revealed that iris damage was associated with the history of complicated glaucoma, and the number of previous intraocular surgeries. The levels of AqH IL-6, IL-8, IL-13, MIP1a, TNF-alpha, and sICAM-1 were significantly elevated in eyes with mild and severe iris damage in phakic eyes, and the levels of AqH IL-8 and sICAM-1 were significantly elevated in eyes with severe iris damage in pseudophakic eyes, compared with the eyes without iris damage (P < 0.045). CONCLUSIONS. Iris damage was associated with the elevation in the levels of aqueous protein and cytokines.