Y2O3:Eu3+ core-in-multi-hollow microspheres were synthesized via a facile hydrothermal method in the presence of glucose followed by a subsequent heat-treatment process. X-ray diffraction (XRD) pattern shows that the as-obtained hollow spheres are cubic phase of Y2O3. Field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) images indicate that the samples are three layer hollow spheres with a diameter of 2-4 microm and the outermost wall thickness of 100 nm, the size of the inner core is about 300-400 nm, and the sub-outer wall thickness is about 100 nm. X-ray energy dispersive spectrum (EDS) shows that the samples are composed of Y, Eu and O. Photoluminescence spectra show that the hollow spheres have a strong characteristic red emission corresponding to the 5D0 - 7F2 transition of Eu3+ ions under ultraviolet excitation. This method can be used to synthesize other rare earth oxide hollow luminescent materials.