High mobility group box-1 protein (HMGB-1), a protein expressed highly in developing neurons, is involved in the development and differentiation of neurons. At the same time, it functions as a transcriptional regulator of particular genes and as a cytokine: HMGB-1 released from a defective cell has been reported to induce damage to the adjacent cells.With a view to examine the relationship between neuronal damage caused by hydrocephalus and HMGB-1, we analyzed the expression of HMGB-1 in the cerebellum, cerebrum, and hippocampus of 1-day-old congenitally hydrocephalic H-Tx rats.As opposed to nonhydrocephalic H-Tx rats, the hydrocephalic H-Tx rats were observed to show stronger expression of HMGB-1 in the cerebellum, cerebrum, and hippocampus. Consequently, the protein was presumed to influence the development of neurons from an early postnatal stage not only in the cerebral cortex and hippocampus but also in the cerebellum, which is less susceptible to the direct effects of hydrocephalus. We expect that, in the future, regulating the expression or functions of HMGB-1 will lead to the possibility of impeding the progress of neuronal damage caused by hydrocephalus.