The liver X receptor (LXR) is a nuclear receptor that acts as a sterol sensor and metabolic regulator of cholesterol and lipid homeostasis. Using a novel LXRα-specific antibody for immunohistochemistry, we evaluated cellular expression of LXRα in fetal rat tissues. In the fetal liver, LXRα-positive macrophages appeared at 12 days and their number peaked at 18 days of gestation. In contrast, hepatocytes expressed LXRα during the later stage of gestation, suggesting the functional development of the liver during ontogeny. Later, macrophages in spleen and thymus expressed LXRα, and some mononuclear cells in the vascular lumen compatible to primitive/fetal macrophages in the fetal circulation were found to express LXRα. In vitro, rat monocytes did not express LXRα, but monocyte-derived macrophages cultured in the presence of macrophage-colony stimulating factor revealed the distinct expression of LXRα in nucleoli. These findings suggest that LXRα plays a role in the differentiation of fetal macrophages, particularly hepatic macrophages, in rat development.