Protease‐activated receptor‐2 (PAR‐2) belongs to a family of G‐coupled receptors activated by proteolytic cleavage to reveal a tethered ligand. PAR‐2 is activated by trypsin and trypsin‐like serine proteases and experimentally, by receptor‐activating peptides (APs), which mimic the tethered ligand. PAR‐2 has recently been implicated in proinflammatory immune responses. For example, PAR‐2−/− mice exhibit markedly diminished contact hypersensitivity reactions and are completely resistant to adjuvant‐induced arthritis. The present study shows that human blood monocytes express low‐level cell‐surface PAR‐2 ex vivo, which is up‐regulated upon cell purification by the mobilization of intracellular stores of PAR‐2 protein. PAR‐2 expression is also present on monocyte‐derived macrophages, but only a small proportion of monocyte‐derived dendritic cells (DC) is PAR‐2+, and blood DC are PAR–. Freshly isolated monocytes responded to the PAR‐2 AP ASKH 95 (2‐furoyl‐LIGKV‐OH) with the generation of a calcium flux and production of interleukin (IL)‐1β, IL‐6, and IL‐8. The results presented thus suggest that PAR‐2 contributes to inflammatory responses by inducing the production of proinflammatory cytokines in peripheral blood monocytes.