Abstract： Objective To study the changes of toll-like receptor 9 (TLR9) signaling transduction in the peri-infarct cortex of rats with middle cercbral artery occlusion (MCAO). Methods The MCAO models were established in 48 SD rats using intraluminal filament method and reperfusion was performed by removing the filament 90 min after occlusion.Sham-operated group was established as controls (n=24).At 6 h,and 3,7 and 14 d after reperfusion,National Institutes of Health of neurological deficit scale was performed; the brain tissues were dyed by TTC staining; the cerebral infarct volumes were measured,and the protein expressions of TLR9,nuclear factor-kappaB (NF-kappaB,P65),tumor necrosis factor-α (TNFα),interferon regulatory factor-7 (IRF7) and interferon-β (IFNβ) in the peri-infarct cortex and contralateral cortex were detected by Western blotting. Results Neurological scale scores and infract volumes of the MCAO rats gradually decreased at 6 h,and 3,7 and 14 d after repeffusion;with the time prolongation,the protein expression of TLR9,IRF7 and IFNβ gradually increased,while the protein expressions of NFκ B (P65) and TNFα ascended first and then descended with the highest expression level at 7 d.The differences of the same protein expressions between each 2 time points were statistically significant (P＜0.05). At the same observation time point, the protein expression in the peri-infarct cortex was significantly higher than that in the contralateral cortex (P＜0.05).The expressions of NFκB (P65) and TNF-α were significantly higher than those of IRF7and IFN-β at 6 h,and 3 and 7 d,respectively; but the results were opposite at 14 h (P＜0.05).These proteins were not detected in the sham-operated group at all time points. Conclusions TLR9 inflammatory pathways and cell protection pathways were activated in ischemic cortex, which may be involved in the process of inflammatory impairment and tissue repair after cerebral infarction.