Abstract: Objective To explore expression changes of amyloid β (Aβ) protein after spinal cord injury in rats and the effect of γ-secretase inhibitordAPT on mechanisms of spinal cord injury in rats. Methods Totally 117 adult SD rats were randomlydivided into three groups: sham group (n=31), spinal cord injury (SCI) group (n=43) and SCI+DAPT (DAPT) group (n=43). Models of spinal cord injury were established by modified Allen's assay, and rats indAPT group were treated with γ secretase inhibitordAPT by gastric tube perfusion before and after SCI procedure. Rats were sacrificed at 6 h, 1d, 3d, 7d, 14d, 21d, 28d after injury. Protein levels of Aβ in serum and cerebro-spinal fluid (CSF) weredetermined by ELISA assay, and content of amyloid precursor protein β (APP), Aβ, Axon growth inhibitory factor receptor (NgR1), Rho related kinase (Rock2) weredetermined by Western blot. Aβ positive cells in injured spinal cord were observed with immunohistochemical analysis, and hind limb motor function of rats was evaluated weekly by BBB (Basso Beattie and Bresnahan) scores. Results Protein levels of Aβ in serum and CSF in SCI group elevated from 6 h (P< 0.05) and reached the peak at 3d post- injury with a time-dependent manner, which was significantly higher than sham group (P< 0.05). Administration ofdAPT led to a significantdecrease of Aβ protein levels in serum and CSF (P< 0.05). Compared with sham group, the protein level of Aβ, NgR1 and Rock2 in SCI group at 3d after spinal cord injury increased significantly (P< 0.05), while itdecreased significantly indAPT group when compared with SCI group (P< 0.05).Immunohistochemical analysis showed that the amount of Aβ positive cells in injured spinal cord increased significantly, and it was significantly less indAPT group than SCI group (P< 0.05), and the BBB score indAPT group was significantly higher than SCI group (P< 0.05). There existed a negative correlation between Aβ levels in serum or CSF and BBB scores in SCI rats (P< 0.05). Conclusion SCI results in elevated expression of Aβ protein in both serum/CSF in spinal cord tissue of rats. Administration ofdAPT leads to an inhibitory effect on expression of Aβ protein and better motor function, which may be related to thedownregulation of NgR1 and Rock2 protein and inhibition of Rho/Rock pathway, thus reducing thedamage of myelin sheath in white matter area.