Objective To explore the protective effect of granulocyte colony stimulating factor (G-CSF) on the activation of microglial in periventricular white matter damage (PWMD) model mice. Methods One-day old newborn mice（n =108）were randomly divided into control group, injury group and treated group. PWMD model was produced by the hypoxia box in the injury group and treated group. Two hours later, the survived mice in the treated group accepted an intraperitoneal injection of rhG-CSF, continued for 7 days. Some mice in 3 groups were sacrificed on day 1, day 3 and day 7 after treatment. The whole brain of the rat was taken for histological analysis and immunofluorescence to observe the accumulation of microglia in vivo and the secretion of cytokines. The periventricular white matter was collected using enzyme-linked immunosorbent assay (ELISA) to detect the level of inflammatory cytokine secretion. The secretion of proinflammatory cytokines and suppression of inflammatory cytokines as well as two types of activated microglia in the number and proportion changes were detected by RT-PCR. The injections of rhG-CSF was finished on day 7 and the neurobehavioral experiments began on day 5, 8, 10, 12 and 30, respectively. The changes of their muscle tone, voluntary movement, and emotional behavior were observed. Results G-CSF facilitated the recruitment of microglia, changed the number and proportion of the M1 and M2 cells in activated microglia, and decreased proinflammatory cytokine secretion as well as increasing the neurotrophic factor secretion. In addition, the recovery of muscle tone, voluntary movement, and sense and motor fuctions were promoted by G-CSF. Conclusion In this study, the administration of G-CSF in the periventricular white matter injury accelerated mouse motor function recovery, improved cerebral palsy symptoms, led the microglia altering to neural protection, and regulated the secretion of inflammatory factors and neurotrophic factors.