〔Abstract〕 Objective To investigate the role of early inhibition of Toll-like receptor 4(TLR4) in regulating hippocampal neuroimmune responseto adolescent ratsafter neonatal hypoxic-ischemic brain damage(HIBD). Methods Postnatal day 7 rats were randomized into controlgroup, hypoxic ischemia(HI)group, and HI+TAK-242(the specific inhibitor of TLR4)(TAK-242) group. The expression of TLR4 in rat hippocampus was detected by immuno-histochemistry at 3 days after HI. Immunofluorescence were used to determine the number of Iba-1+, GFAP+,CD161+, MPO+and CD3+cells in the hippocampus at 21 days after HI. Immunohistochemistry was used to detect ICAM-1 and C3 a expression in the hippocampal CA1 region; and Western blot was used to detect tumor necrosis factor interleukin IL-1β, TNF-α and IL-10 expression.Results Compared with control group, significantly raised TLR4 expression was observed in the left hippocampal CA1, CA3 and DG regions(P<0.01 or P<0.05), while the expression in the TAK-242 group lowered compared to the HI group(P<0.05). The number of GFAP+cells in the CA1 area of the hippocampus in the TAK-242 group of neonatal rats decreased compared to which in the HI group at 21 days after HI(P<0.05),but the number of CD3+T lymphocytes in the hippocampal CA1 area of new born rats in the HI group increased compared to which in the Control group(P<0.05), but the difference between TAK-242 and the Control group was not statistically significant. The number of Iba-1+cells, MPO+cells, CD161+cells, the expression of ICAM-1 and C3a in hippocampal CA1 region, and the expression of TNF-α, IL-1β and IL-10 in hippocampus of rats were not different among groups at 21 days after HIBD.Conclusion Early inhibition of TLR4 may ameliorate adolescent neuroimmune disorders by reducing the increase of hippocampal astrocytesafter neonatal HIBD.