Exosome vesicles (EVs) released by macrophages are potential biomarkers for the analysis of immune responses. This study reports a high-throughput EV detection assay developed using a label-free EV microarray. The EV microarray consists of a panel of seven antibodies that are specific to multiple membrane receptors of the target EVs. The EV microarray was fabricated on a photonic crystal (PC) biosensor surface. The hyperspectral imaging approached was implemented to quantify the antibody and EV absorptions on the PC-based microarray. The label-free EV microarray enables low-cost, rapid, and high-throughput characterization of macrophage EVs with a significantly reduced sample volume of 1 μL.