The bacterial cellulose (BC) secreted by G. xylinus is a network of pure cellulose nanofibers, which has high crystallinity, wettability and mechanical strength. These characteristics make BC an excellent material for tissue engineering constructs, noteworthy for artificial vascular grafts. In this work, the in vivo biocompatibility of BC membranes produced by two G. xylinus strains was analyzed through histological analysis of long-term subcutaneous implants in the mice. The BC implants caused a mild and benign inflammatory reaction that decreased along time and did not elicit a foreign body reaction. A tendency to calcify over time, which may be related to the porosity of the BC implants, was observed, especially amo the less poro s BC-1 implants. In addition, the potential toxicity of BC nanofibers - obtained by chemical-mechanical treatment of BC membranes - subcutaneously implanted in mice was analysed through bone marrow flow cytometry, blood and histological analyses. After 2 and 4 months post implantation, the nanofibers implants were found to accumulate cytoplasmically, in subcutaneous foamy macrophages aggregates. Moreover, no differences were observed between the controls and implanted animals in thymocyte populations and in B lymphocyte precursors and myeloid cells in the bone marrow.