Objective To examine the expression of Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-α) and interferon-β (IFN-β) in the brain of rabbits with subarachnoid hemorrhage (SHA), and investigate the mechanisms of TLR4 signaling pathway in the early brain damage following SAH.Methods The SAH model of rabbits were prepared by injecting autologous arterial blood into the cisterna magna.A total of 36 rabbits were randomly divided into three groups: control, SAH and E5564 treatment (n=12 each).Normal saline and autologous arterial blood were injected into the cisterna magna in the control and SAH groups respectively.In the E5564 group, Eritoran (1.5 mg/kg) was administerd by vein injections (twice) after SAH inducement.The neurologic deficits were determined every day.The expression levels of TLR4, TNF-α and IFN-β mRNA in the hippocampus were measured by real-time quantitative PCR.Results The expression of TLR4, TNF-α and IFN-β mRNA in the SAH group was significantly higher than in the control group (P<0.05).The E5564 group showed obviously decreased the excpression of TLR4, TNF-α and IFN-β mRNA compared with the SHA gyoup (P<0.05).The neurologic deficits were improved in the E5564 group compared with the SAH group (P<0.05).Conclusions TLR4 may play a crucial role in the brain damage following SAH.The mechanisms may be associated with the TLR4 signaling pathway.E5564 may attenuate the brain damage following SAH by inhibiting TLR4.