The main function of CD163 (hemoglobin scavenger receptor) is to bind the hemoglobin-haptoglobin complex, thereby mediating extravasal hemolysis. However, CD163 also has an antiinflammatory function. After CD163-mediated endocytosis, hemoglobin is catabolized further by hemeoxygenase 1 (HO-1). Previously, we found expression of HO-1 to be restricted to microglia/macrophages at sites of hemorrhages in human traumatic and ischemic brain lesions. We now investigated if CD163 expression is also correlated with hemorrhages in brain lesions. Methods. Autopsy brain tissue from 44 cases with hemorrhagic brain lesions (32 traumatic brain injuries/TBI, 12 intracerebral bleedings/ICB), 56 non-hemorrhagic brain lesions (30 ischemias, 26 hypoxias) and 6 control brains were investigated. The post injury survival times ranged from a few minutes to 60 months. Results. In controls, single perivascular monocytes expressed CD163, but only single CD163+ microglia were found in 3/6 cases. CD163+ cells in the parenchyma (activated microglia/macrophages) increased significantly within 24 hours after trauma and ischemia and within 1-7 days following ICB or hypoxia. Overall, significantly lower and higher levels of parenchymal CD163+ cells occurred in hypoxia and ischemia, respectively. Perivascular CD163+ cells also increased significantly in all pathological conditions. In areas remote from circumscribed brain lesions (TBI, ICB, ischemia), significant changes were only found in ICB and ischemia. Conclusions. De novo expression of CD163 by activated microglia/macrophages and CD163+ infiltrating monocytes are neither restricted to nor predominant in hemorrhagic brain lesions. Thus, the antiinflammatory function of CD163 probably predominates, both in hemorrhagic and non-hemorrhagic brain lesions and points to possible immunomodulatory treatment strategies targeting CD163.