Emu oil is derived from the emu (Dromaius novaehollandiae), which originated in Australia, and has been reported to have anti-inflammatory properties. Inflammation was induced in anesthetized CD-1 mice by applying 50 microL of 2% croton oil to the inner surface of the left ear. After 2 h, the area was treated with 5 microL of emu, fish, flaxseed, olive, or liquified chicken fat, or left untreated. Animals were euthanized at 6 h postapplication of different oils, and earplugs (EP) and plasma samples were collected. Inflammation was evaluated by change in earlobe thickness, increase in weight of EP tissue (compared to the untreated ear), and induction in cytokines interleukin (IL)-1alpha and tumor necrosis factor-alpha (TNF-alpha) in EP homogenates. Although reductions relative to control (croton oil) were noted for all treatments, auricular thickness and EP weights were significantly reduced (-72 and -71%, respectively) only in the emu oil-treated group. IL-1alpha levels in homogenates of auricular tissue were significantly reduced in the fish oil (-57%) and emu oil (-70%) groups relative to the control group. The cytokine TNF-alpha from auricular homogenates was significantly reduced in the olive oil (-52%) and emu oil (-60%) treatment groups relative to the control group. Plasma cytokine levels were not changed by croton oil treatment. Although auricular thickness and weight were significantly correlated with each other (r = 0.780, P < 0.003), auricular thickness but not weight was significantly correlated with cytokine IL-alpha (r = 0.750, P < 0.006) and TNF-alpha (r = 0.690, P < 0.02). These studies indicate that topical emu oil has anti-inflammatory properties in the CD-1 mouse that are associated with decreased auricular thickness and weight, and with the cytokines IL-1alpha and TNF-alpha.