In order to examine the influence that shape and chemistry of different materials have on the incitement of a tissue reaction, we implanted five materials (the two metals Ni and Co, the two ceramics TiO2 and SiO2, and the polymer poly vinyl-chloride) as nanoparticles or bulk, in the dorsal muscles of 50 rats. After 6 or 12 months, rats were euthanized and the implanted materials were excised together with the surrounding tissue. After a first histological evaluation, the specimens were prepared for environmental scanning electron microscopy (ESEM) and for energy dispersive spectroscopy (EDS), in order to analyse the chemical composition of the implanted material after the biological interaction had occurred, and to evaluate the possible corrosion and diffusion of the materials at tissue interface. The results indicate that the metals at nanoscale size have a carcinogenic effect, while the bulk materials only induce a foreign-body reaction. The ESEM observations show a chemical transformation of the materials. Corrosion of the metals and subsequent recombination of the released ions in a sort of organic-inorganic crystals is showed and verified by the EDS analyses. Finally, our hypotheses of the involved pathological mechanism are suggested.