The interfacial reactions and interdiffusion between Al2O3 and Ti-24Al-11Nb (at%) alloy have been investigated. Diffusion couples were fabricated by thermal sprayed Al2O3 film onto Ti-24Al-11Nb substrate, and then annealed at 1200°C. Interfacial layers were characterized using electron probe microanalysis (EPMA), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The layered structure of interface region was observed which showed the diffusion controlled characteristics. In the reaction zones, the reaction products consisted mainly of TiO, TiO2, and Al2TiO5. Adjacent to the reaction zones, there existed β phase free zone and β phase lacking zone. The β phase free zone resulted from Nb depletion of this region. The reaction mechanism has been discussed using thermodynamic approach.