Luteolin (1), a natural product occurring in many vegetables and fruits, is known to have several biological activities. Cluster for differentiation (CD) families, such as CD11b, -14, and -36, are expressed during pathological processes of atherosclerosis and are used broadly as markers of monocytic differentiation into macrophages. Herein, it was investigated whether 1 and three other flavonoids [chrysin (2), apigenin (3), and tricetin (4)] blocked 12-O-tetradecanoylphorbol 13-acetate (TPA)-triggered induction of CD families, which were induced through the activation of protein kinase C (PKC), mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK), and NADPH oxidase (NOX)-derived reactive oxygen species (ROS). When compared to flavonoids 2-4, 1 blocked TPA-triggered induction of CD families and cell adherence of monocytic THP-1 cells. Luteolin completely blocked intracellular ROS generation, whereas it did not inhibit MEK/ERK phosphorylation. Moreover, pretreatment with 1 suppressed TPA-triggered induction of NOX2 and membrane translocation of p47phox. Overall, it is revealed that 1 suppresses TPA-triggered induction of CD families by the prevention of NOX2 activation. © 2013 The American Chemical Society and American Society of Pharmacognosy.