Low density lipoprotein receptor‐related protein (LRP) participates in the uptake and degradation of several ligands implicated in neuronal pathophysiology including apolipoprotein E (apoE), activated α₂ ‐macroglobulin (α₂M*) and β‐amyloid precursor protein (APP). The receptor is expressed in a variety of tissues. In the brain LRP is present in pyramidal‐type neurons in cortical and hippocampal regions and in astrocytes that are activated as a result of injury or neoplasmic transformation. As LRP is expressed in the monocyte/macrophage cell system, we were interested in examining whether LRP is expressed in microglia. We isolated glial cells from the brain of neonatal rats and LRP was immunodetected both in microglial cells and in astrocytes expressing glial fibrillar acidic protein (GFAP). Microglial cells were able to bind and internalize LRP‐specific ligand, α₂M*. The internalization was inhibitable by RAP, with a Kd of 1.7 nM. The expression of LRP was up‐regulated by dexamethasone, and down‐regulated by lipopolysaccharide (LPS), gamma interferon (IFN‐γ) or a combination of both. LRP was less sensitive to dexamethasone in activated astrocytes than in microglia. We provided the first analysis of LRP expression and regulation in microglia. Our results open the possibility that microglial cells could be related to the participation of LRP and its ligands in different pathophysiological states in brain. J. Neurosci. Res. 60:401–411, 2000 © 2000 Wiley‐Liss, Inc.