Abstract: Monocytes as well as other professional Antigen Presenting Cells (APC), Dendritic Cells (DC) and macrophages, play a critical role in adaptive and innate immune responses. A Differential Detergent Fractionation (DDF) analysis was conducted on avian monocytes to reveal proteins related to cell adhesion, uptake and antigen presentation to lymphocytes, receptor proteins, proteases and cytokines. We identified a total of 3,229 proteins with 46 of these involved in the functions of professional APC. Of these proteins, fourteen were receptor proteins, four were related to antigen presentation (including MHC Class I), six to antigen uptake, ten to cell adhesion, two Toll-like receptors (TLR 4 and 15) and nine protease proteins were identified. This research demonstrates that the DDF approach provides meaningful, interpretable, functional, information concerning protein expression profiles associated with monocyte activation and differentiation into macrophages and/or immature DC in avian species. This data will be instrumental in future experiments evaluating protein expression of monocytes in stressed broilers.