Objective To explore the change of Toll-like receptor 4(TLR4) expression in microglia after compression injury in the spinal cord of rats, and to compare the distribution of TLR4 positive cells with the area of injury and immunoglobulin G (IgG) extravasation at different time points. Methods Spinal cord compression injury was made at T8 segment in 48 adult male SD rats, and the rats were randomly divided into 6 groups. Sham and injured animals were fixed by perfusion of 4% paraformaldehyde, 2 cm of the spinal cord blocks with compressed site in center were then removed at 0 hour, 3 hours, 24 hours, 72 hours and 7 days after injury. Frozen sections were made for HE and immunofluoresent staining to detect the injury area and the expression of TLR4 in the spinal cord. The distribution of TLR4 positive cells, the injury area and the extravasated IgG were compared as well. The number of TLR4 positive microglial cells was counted by using Image Pro Plus 6.0 software. BR> Results TLR4 was mainly expressed in microglial cells and the expression started to increase between 3 hours and 24 hours, and peaked at 72 hours after the spinal cord compression injury, then descended at 7days, according to the number of TLR4-positive microglia. The distribution of TLR4 immunoreactive product was consistent with the area of injury and that of extravasated IgG. Conclusion In the rat model of spinal cord compression injury, TLR4 expressed in microglial cells may play an important role in the secondary injury and TLR4 expression may associate with the compromise of blood-spinal cord barrier. BR>