Abstract: Objectives　To study the mechanism of brain damage caused by Staphylococcus epidermidis (SE) in mice. Methods  A total of 80 neonatal mice of postnatal day 1 (PND1) were divided into SE group (48 mice), normal saline (NS) group (16 mice) and control group (16 mice). Mice in SE group were intravenously injected with 50 μl SE (108/ml). Mice in NS group were given 50 μl NS. Mice in control group were not intervened. At different time points after SE injection (6 h, 24 h, 72 h, 5 d, 7 d), the CFU of brain, blood, and spleen were calculated. Serial sections of paraffin-embedded brain tissue were used for detection of ionized calcium-binding adaptor moleculor1 (Iba-1) by immunohistochemical staining. The positive cells were calculated. ELISA was used to measure the levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-5 (IL-5), interleukin-6 (IL-6) of brain at 6 h and 24 h after SE injection. Results  There was no SE in brain in different time points. The CFU was at the highest level at 6 h and then decreased after 24 h in blood and spleen. The Iba-1 positive cells in SE group were significantly increased compared to NS group and control group at 24 h and 72 h (P<0.05). There was no difference of Iba-1 positive cells between 24 h and 72 h after SE injection (P>0.05). The levels of TNF-α, IL-1β, IL-5, and IL-6 were significantly higher in SE group than those in NS and control at 6 h and 24 h (P<0.05). The levels of TNF-α, IL-1β, IL-5, and IL-6 were significantly lower in SE group at 24 h than those in SE group at 6 h (P<0.01). Conclusions  It is suggested that cytokines produced by microglias may be the mediators of SE-caused brain damage.