Swelling of astrocytes at early stage of cerebral ischemia has been reported, however, the fate and the cell death pathway of astrocytes are still unclear. Focal cerebral ischemia was induced in Sprague-Dawley rats by permanent occlusion of middle cerebral artery for 3 to 48 h. Haematoxylin and eosin (HE) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), glial fibrillary acidic protein (GFAP), caspase-3 immunostaining, and double-staining with TUNEL and GFAP were carried out on consecutive sections. The ultrastructure was revealed by electron microscopy. Using electron microscope, apoptotic neurons were confirmed with condensed chromatin and apoptotic bodies. In the core of the infarct, clumps of heterochromatin around the edge of nucleus, vacuolar degeneration of the nucleus and leakage of chromatin were demonstrated at 3, 6, and 12 h respectively in the swelling astrocytes, which accorded with the process of oncosis; in the peripheral zone of the infarct, reactive astrocytes with nuclear membranes preserved demonstrated increased cell size and number and coexisted with oncotic astrocytes. Scattered GFAP-positive cells and ubiquitous caspase-3-positive cells were found in the core after 12 h following cerebral ischemia, and no cells positive for double-staining with TUNEL and GFAP were found in the ischemic regions, indicating that most GFAP-positive astrocytes did not die by apoptosis. Findings from present study demonstrate that after cerebral ischemia, oncosis may be the possible cell death pathway of astrocytes in the ischemic region, and oncotic astrocytes coexist with reactive astrocytes in the peripheral zone.