The aim of this study was to explain differences in the biological behaviour of two boron carbide powders prepared by different synthesis methods. The commercial powder HD had a lower boron content in comparison to the synthesized powder SP. The analysis both powders surface confirmed the higher content of B-C bonds but the presence of heteroatomic B-C-O bonds indicating the oxide passivation of the surface of particles of only HD powder. On the other hand, the SP powder contains more boron in the volume as well as on the surface of particles. These differences facilitated the interaction between the carbide particles with the proteins in the culture medium. Proteins from the culture medium and active collagen peptides were more easily adsorbed to the surface of the synthesized powder particles, which was evidenced by new bands appearing in the spectrum. This translated into an increasing hydrophilicity of the synthesized boron carbide powder. The presence of proteins on the surface of the powder facilitated the cells adhesion of macrophages and fibroblasts. The synthesized boron carbide powder improved the macrophage functional status; the cells were characterized by high viability and low cytotoxicity as well as the correct morphology.