Objective To explore the effects of early maternal separation on the cognitive function in adult male rats， and the involvement of inflammatory factors in hippocampus， to reveal the mechanistic role of early life stress in neuronal plasticity. Methods New born SD rats were randomly divided into maternal separation（ MS） group and control（ NMS） group. Maternal separation was carried out from Day 3 to Day 22，3 hours per day in MS group. There was no treatment in the NMS group. At the age of 10 weeks， Morris Water Maze was chosen to compare the behavioral deficits in adulthood between each group. NeuN immunofluorescent was used to calculate the normal neurons amounts in Dentate Gyrus（ DG） rejion. GFAP/Iba-1 immunofluorescent was applied compare the amounts of astrocytes and microglias. Ki67/DCX immunofluorescent was select to observe the proliferation and differentiation of neurons in Dentate Gyrus， Western Blot was performed to detect the levels of IL-1β， IL-6 and TNF-α. Results Morris Water Maze findings showed that MS group rats had learning and memory declines， reflected by longer escape latency， less time in objective quadrant and fewer cross objective times （P＜ 0.05） relative to NMS group rats. There was no significant change in the number of normal and degenerated neurons in DG region of hippocampus（ P＞0.05）. However， the number of astrocytes and microglias increased （P＜0.01）. The expression of IL-1β and TNF-α in hippocampus increased（ P＜0.01）， while the expression of IL-6 did not change significantly（ P ＞ 0.05）. Conclusions Repeated early life maternal separation could induce neuroinflammatory response in rat hippocampus. The increased the number of astrocytes and microglia and the increased expression of inflammatory cytokines in hippocampus lead to cognitive changes in adult rats.