Aquaporin 4(AQP4) is a water channel protein strongly expressed in the central nervous system in perimicrovessel astrocyte foot processes, the glia limitans, and ependyma. Expression of AQP4 is highest at the blood-brain barrier and blood-spinal cord barrier, supporting its critical function in material transport across these structures. Recently, presence of the anti-aquaporin-4 antibody in sera has been used as an important diagnostic tool for neuromyelitis optica, suggesting a potential role in central nervous system inflammation. The aim of the present study was to examine AQP4 protein expression in the cerebellum and spinal cord from rats with experimental autoimmune encephalomyelitis. By western blot analysis, AQP4 expression increased during experimental autoimmune encephalomyelitis development, and peaked at onset (lumbar enlargement) or climax (cerebellum) of neurological signs of experimental autoimmune encephalomyelitis. There was also a faster and more pronounced increase in permeability in the cerebellar blood-brain barrier and the lumbar enlargement blood-spinal cord barrier consistent with AQP4 expression, which was manifested by increased Evans Blue leakage and reduced tight junction protein expression. In conclusion, aquaporin upregulation may be involved in the development of inflammation in the acute phase of experimental autoimmune encephalomyelitis, and may correlate with damage to central nervous system barrier function. Anat Rec, 294:46-54, 2011. (C) 2010 Wiley-Liss, Inc.