Radiation-induced changes in the parietal cortex of Wistar rats were observed at various time points after gamma surgery. Maximum dosages of 50, 75, and 120 Gy were given at the iso-center of the radiation using a 4-mm collimator. Conventional histochemical and immunocytochemical analyses, and computer-assisted videomicroscopy were utilized to examine perfusion-fixed brain tissue. Irradiation at a dosage of 50 Gy elicited morphological changes of astrocytes in the parietal cortex at 3 months. Vasodilatation became obvious at 12 months; fibrin deposition was observed in the dilated capillary wall. Neither leakage of Evans Blue from the vasculature into the tissue nor necrosis was observed across the 12 month observation period. Irradiation at a dosage of 75 Gy resulted in morphological changes of astrocytes within 1 month. Dilatation of vessels and capillary thickening were observed at 3 months. Evans Blue leakage and necrosis were observed at 4 months after 75 Gy irradiation. At this time, the walls of arterioles became thickened by subintimal accumulation of fibrin and hyaline substance; this sometimes resulted in occlusion of the lumen. Significant hemispheric swelling was observed at 4 months. Irradiation at a dosage of 120 Gy elicited changes in astrocytic morphology within 3 days. Evans Blue leakage into the tissue was observed by 3 weeks. Vasodilation became marked at this time point and rarefaction was observed in the irradiated cortex. Necrosis was observed at 4 weeks, however, no significant swelling was observed. Taken together, these findings demonstrate time-dependent and dosage-dependent changes in normal cerebral tissue after Gamma Knife irradiation. These results provide a basis for gauging the impact of gamma surgery in regions of eloquent tissue. An enhanced understanding of the cellular responses to radiosurgery will contribute to developing and evaluating future applications for gamma surgery.