The aim of this work was to study the behaviour of zinc-doped phosphosilicate glasses based on Bioglass 45S5. In vitro (in simulated body fluid), the reactivity was analysed by means of inductively coupled plasma spectrometry, environmental scanning electron microscopy-energy-dispersive spectroscopy (ESEM-EDS) and X-ray diffraction. In vivo (a rat implanted with glass), the reactivity and the tissue behaviour were analysed by conventional histology, histochemistry, microradiography and ESEM-EDS. The in vivo behaviour matches that in vitro perfectly; they show comparable glass degradation processes and rates, ruled by the amount of zinc in the glass. The reaction mechanism for the formation of a polymerized silica layer superimposed with a peripheral calcium phosphate layer is clearly substantiated by ESEM-EDS investigations. The crystallization of a biologically active hydroxyapatite (HA) layer is observed in both cases; the in vitro experiment shows the presence of HA after 4 days.