To investigate the possible relationship between allergy and otitis media with effusion (OME), we investigated the cytokine level in the middle ear effusion (MEE)s of children with persistent OME. Interleukin (IL)-2, IL-4, IL-6 and tumor necrosis factor (TNF)-alpha in the MEEs were measured by devised sensitive sandwich enzyme-linked immunosorbent assay (ELISA) and compared allergy positive group with allergy negative group. The mean levels of IL-4, IL-6 and TNF-alpha in MEE were significantly higher in allergy positive group than allergy negative group (P<0.05). Elevation of Th-2-driven cytokines (IL-4, IL-6) and TNF-alpha in MEEs may be a contributing factor in the persistence of OME with allergy.