Tenascin is a large extracellular matrix glycoprotein characterized by its spatiotemporal expression during embryogenesis, carcinogenesis and wound healing. Unfortunately, disruption of the tenascin gene does not induce an obvious abnormality during development, and its functionin vivo remains unclear. Here we investigated to determine whether tenascin is involved in inflammatory responses in tenascin knockout mice. Epicutaneous application of a hapten, 2,4-dinitrofluorobenzene, to the ear skin of the normal mouse caused the dermatitis and induced the expression of tenascin. In the tenascin knockout mice, the dermatitis was much more severe than in normal mice, accompanied by disorganization of extracellular matrix. These results suggest the protective role of tenascin in vivo during the inflammatory responses.