Studies in the authors' laboratory have recently demonstrated the presence of potent inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) in human middle ear effusions. The clinical significance of this finding has not been fully elucidated because of the limitations of human studies. We hypothesized that the chinchilla model of otitis media may be an appropriate system with which to study the role of cytokines in otitis media with effusion. To begin to investigate this possibility, 30 chinchillas underwent surgical blockage of the eustachian tube (ET) to promote effusion development. After 2 weeks, examination by otoscopy demonstrated 27 ears to have developed an effusion. Next, all middle ear clefts, in random manner, were either injected with heat-killed Streptococcus pneumonias 1 ± 106 in 0.1 mL normal saline, injected with 0.1 mL normal saline alone, or received no injection at all. Middle ear effusions were obtained and analyzed for IL-1β and TNFα by enzyme-linked immunosorbent assay (ELISA). This study demonstrated a significant correlation between IL-1β and the presence of an effusion (P<.001). Additionally, increased TNFα levels correlated with bacterial component presence (P<.001), i.e, mean TNFα level was 108, 10.8, and 0 pg/mL in bacteria, normal saline, and noninjected ears, respectively. These findings would suggest that cytokine expression may relate to specific pathological conditions and that the chinchilla model for otitis media with effusion (OME) could be used to further explore the role of cytokines in OME.