Objective Through establishment of brain slice model in rats with perfusion and oxygen glucose deprivation (OGD), we investigated whether this model can replicate the pathophysiology of brain injury in cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) or not and whether perfusion and OGD can induce preoligodendrocytes (preOL) injury or not, to provide cytological evidence for white matter injury after cardiopulmonary bypass. Methods Three to five living brain slices were randomly obtained from each of forty seven-day-old (P7) Sprague-Dawley (SD) rats with a mean weight of 14.7±1.5 g. Brain slices were randomly divided into five groups with 24 slices in each group: control group with normothermic artificial cerebralspinal fluid (aCSF) perfusion (36℃) and DHCA groups: OGD at 15℃, 25℃, 32℃ and 36℃. The perfusion system was established, and the whole process of CPB and DHCA in cardiac surgery was simulated. The degree of oligodendrocyte injury was evaluated by MBP and O4 antibody via application of immunohistochemistry. Results In the OGD group, the mature oligodendrocytes (MBP-positive) cells were significantly damaged, their morphology was greatly changed and fluorescence expression was significantly reduced. The higher the OGD temperature was, the more serious the damage was; preOL (O4-positive) cells showed different levels of fluorescence expression reduce in 36℃, 32℃ and 25℃ groups, and the higher the OGD temperature was, the more obvious decrease in fluorescence expression was. There was no statistically significant difference in the O4-positive cells between the control group and the 15℃ OGD group. Conclusion The perfused brain slice model is effective to replicate the pathophysiology of brain injury in CPB/DHCA which can induce preOL damage that is in critical development stages of oligodendrocyte cell line, and reduce differentiation of oligodendrocyte cells and eventually leads to hypomyelination as well as cerebral white matter injury.