Within hours after hypoxic ischemic (HI) brain injury in the 7-day-old(PD7) rat, histochemically stainable iron accumulates in areas of neuronal injury. We have found that the increased iron staining persists for at least 3 weeks. Iron is a potent inducer of oxidative injury and could contribute to continued brain injury or inflammation. It is not known how long the abnormal iron accumulation persists or what its effect might be on surrounding brain parenchyma. Objective: The aim of this study was to examine the long-term effects of HI brain injury on the distribution of iron staining in the neonatal rat. Methods: A HI insult to the right hemisphere of PD7 rats was induced by permanently ligating the right common carotid artery then subjecting the pups to hypoxia in 8% O2 for 2.25hrs. Some pups (n=4 per group) were killed at 2, 6, or 9months of recovery. Iron staining was performed with the intensified Perls stain on 40micron thick floating brain sections from 4% paraformaldehyde perfused rats. Selected sections were also examined by electron microscopy. Specific cell identification markers were used to identify astrocytes and microglia. Results: At 2months of age, iron stained microglia were numerous around cavitations in the cerebral cortex. The white matter tracts were relatively weakly stained for iron compared to normal age matched rats and iron loaded microglial cells persisted in the subcortical white matter. Non-cellular deposits of iron occurred occasionally in the striatum and only in the ligated hemisphere. By 6months of age the most striking observation was 'plaque' like structures in the hippocampus and corpus striatum that stained positive for iron. The 'plaques' were surrounded by iron positive cells. Electron microscopy of the 'plaques' showed large dense non-filamentous structures with a layered core. The 'plaques' were still seen at 9 months of age. They were not observed in animals under 30days of age. They are only seen in the HI side of the brain and not found in normal animals. Microglia and astrocytes surrounded the 'plaques'. Conclusion: HI injury in the first week of life manifests as a changing distribution of iron in the brain for at least 9 months in rats. The altered iron staining of the white matter suggests a disturbance in myelination. The appearance of 'plaque' like structures in the striatum is a late manifestation and suggests that the response to injury in newborn rats evolves over months.