Angiostrongylus cantonensis causes severe central nervous system (CNS) infection leading to chronic demyelinating disease. The biological role of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) in myelin-related disease requires investigation. CNP expression was investigated in the brain of mice at six time points 5-25 days post-inoculation with A. cantonensis. CNP was measured in brain tissue by quantitative reverse transcription polymerase chain reaction and by western blotting in the cerebrospinal fluid (CSF). The concentration of CNP in the CSF was significantly up-regulated during the severe phase of meningoencephalitis or meningitis as compared with controls. Immunohistochemical labelling localized CNP expression to the cytoplasm of oligodendrocytes. These results suggest that CNP in the CSF from mice with angiostrongylosis is an indicator of myelin destruction. Therefore, measurement of CNP in the CSF of patients with eosinophilic meningitis may be useful in clinical management.