Periventricular leukomalacia (PVL) is due to oligodendrocyte (OL) injury and hypomyelination associated with hypoxia/ischemia (H/I) and systemic inflammation in premature infants. Using immature rodent model of H/I white matter (WM) injury, we shown that early OL injury occurs due to glutamate-receptor mediated toxicity and can be attenuated by AMPAR antagonists (Follett, J. Nsci, 2004). Activated microglia play an active role in the inflammatory response following the cerebral injury, and we showed a steady increase in microglia 24–72 hrs following H/I (Samonte, SFN Abs, 2004). In this study, we examined in the same model the protective efficacy of the microglial inactivator minocycline administered post H/I. Postnatal day 6 Long-Evans rats underwent left carotid artery ligation, followed by a hypoxia (1hr, 6%O2), and were randomly divided into minocycline-treated (n=8) and control groups (n=8). Minocycline treatment (50mg/kg i.p.) was initiated immediately following H/I and continued every 12 hrs. The co...