CuO microspheres with hollow interiors were synthesized by a simple method using urea as an important reagent to generate soft-template. X-ray diffraction pattern, Infrared spectrum, electronic diffraction, field emission scanning electron microscopy images, transmission electron microscopy images and high-resolution transmission electron microscopy investigated the phase structures and morphologies of CuO microspheres. The hollow spheres may be formed through the assembling of nanoparticles with the assistance of gas bubbles and a self-generated template and aggregation process was proposed for the formation mechanism of the CuO spheres.