A possible complication associated with the implantation of HA-based prosthesis is the release of particles. Those particles can be phagocyted by monocytes that are among the first cells to colonize the inflammatory site. The activated monocytes produce inflammatory mediators such as cytokines that cause osteoclasts activation. The present work studies the effect of zinc-substituted hydroxyapatite particles with various concentrations of zinc on cytokines production (TNF-α, IL-1β, IL-6, IL-10, and IL-8) by human monocytes LPS-stimulated or not. The concentrations used were 0.5%, 1%, 2%, and 5%. Our data demonstrates that the zinc has an effect on cytokines production. It decreases the production of TNF- α and increases the production of IL-8 by unstimulated cells. Using LPS-stimulated cells, it decreases the production of inflammatory cytokines and increases the production of anti-inflammatory cytokine (IL-10). So zinc-substituted hydroxyapatite has favourable effects on the cytokines production by monocytes.