Sol-gel derived glasses based on SiO2-CaO were studied with and without Zn as doping element. Investigations of their in vitro bioactivity were performed by soaking the glass powders in biological fluids for time periods up to 4 days. The surface reactions were characterized at the micrometer scale and with a high level of efficiency for both major and trace elements by using Particle Induced X-ray Emission (PIXE) associated to Rutherford Backscattering Spectroscopy (RBS). The evolution of the biological medium composition was followed by ICP-AES analyses. If the bioactivity of binary SiO2-CaO glasses is already known, this study shows the improvement of the early step of the bioactive process by using zinc as a doping element. Indeed, zinc improves the specific surface area and then the number of sites for the nucleation of calcium phosphate precipitates. In addition, Zn-doping slows the glass dissolution and enhances the calcium phosphate layer growth at the surface of the ZnO-SiO2-CaO glass which is a prerequisite for bioactive glasses to bond to living bone.