Using light and electron microscopy, we studied the interaction between lipids and host tissue for up to 15 days after experimentally produced cerebral infarcts in 16 rats. A lipid-dense zone was formed along the periphery of the infarcts before a glial response started; a glycogen-rich zone appeared peripheral to the lipid zone. Macrophages and astrocytes then started to proliferate in the lipid and glycogen-rich zones. The cerebral tissue within the lipid zone underwent complete necrosis. Ultrastructurally, lipids were observed in the edematous areas as well as in various types of hematogenous and resident cells. Glycogen granules were present mainly in the astrocytic processes. Macrophages rapidly evolved into foamy macrophages in the central necrotic areas, whereas foamy transformation was not striking in the peripheral, less injured areas. Reactive fibrous astrocytes also contained varying amounts of lipids. The exact biologic significance of the lipid zone in the premacrophagic stage remains unclear; however, since lipids are hydrophobic, they may function as a barrier against edema fluid extension into the adjacent tissue.