The development of central pontine myelinolysis was studied in rats. Severe hyponatraemia was induced using vasopressin tannate and 2.5% dextrose in water and then rapidly corrected with hypertonic saline alone, hypertonic saline and dexamethasone simultaneously, or hypertonic saline plus dexamethasone 24 h later. The permeability of the blood-brain barrier was evaluated using the extravasation of Evans blue dye and the expression of inducible nitric oxide synthase (iNOS) in the brain was examined using Western blot analysis. Histological sections were examined for demyelinating lesions. In rats receiving hypertonic saline alone, Evans blue dye content and expression of iNOS began to increase 6 and 3 h, respectively, after rapid correction of hyponatraemia and demyelinating lesions were seen. When dexamethasone was given simultaneously with hypertonic saline, these increases were inhibited and demyelinating lesions were absent. These effects were lost if dexamethasone injection was delayed. Disruption of the blood-brain barrier and increased iNOS expression may be involved in the pathogenesis of central pontine myelinolysis, and early treatment with dexamethasone may help prevent the development of central pontine myelinolysis.