Objective— Liver X–activated receptor α (LXRα) regulates multiple genes controlling cholesterol metabolism and transport. To clarify its role in atherogenesis, we established a monoclonal antibody recognizing native human LXRα protein and studied the expression pattern in human atherosclerotic lesions. Methods and Results— A novel monoclonal antibody PPZ0412 was raised against the ligand-binding domain of LXRα, which can be used for immunostaining of human LXRα protein. LXRα protein was detected in the nucleus of macrophages in the liver, spleen, or lung and also in hepatocytes and adipocytes. In atherosclerotic lesions, the LXRα protein was detected in macrophages positive for scavenger receptor class A and/or CD68. Conclusions— In the human body, the LXRα protein is highly expressed in macrophage lineage cells and foam cells in atherosclerotic lesions and is identified as a target for intervention in atherosclerotic disease.