Abstract: Objective To investigate the alteration of NF-B(p65) in the brain tissue of scrapie-139A infected mice and its mechanism. Methods Western blot and immunohistochemistry (IHC) were conducted to analyze the expression level of p65 in the brain tissue of scrapie-139A infected mice. Immunofluorescent analyses were performed to study the distribution of p65 in neuron and glia. Results The level of p65 in the brains of scrapie-139A infected mice at terminal stage decreased-significantly. Dynamic analysis indicated that p65 levels in 139A infected mice brains increased at early stage and then decreased gradually. IHC analyses showed the level of p65 in the brains of scrapie-139A infected mice at terminal stage decreased significantly. Immunofluorescent analyses showed that p65 colocalized with the NeuN-positive cells in the brains of both normal and scrapie infected mice at terminal stage. Conclusion NF-B(p65) was mainly distributed in neurons of the central nervous system, and the level of p65 in the brains of scrapie-139A infected mice at terminal stage decreased-significantly, suggesting that NF-B(p65) had changed in the brain tissue of scrapie infected mice, which might play a role in disease progression.