Propentofylline (PPF) is a xanthine derivative with pharmacological effects distinct from those of the classical methylxanthines. It depresses activation of microglial cells and astrocytes which is associated with neuronal damage during neural inflammation and hypoxia. The aim of this study was to evaluate whether PPF had the capacity of affecting glial cells behavior during the process of demyelination and remyelination following ethidium bromide (EB) gliotoxic injury. EB injection into the CNS is commonly used as an experimental demyelinating model inducing local oligodendroglial and astrocytic death, which results in primary demyelination, blood–brain barrier and glia limitans disruption and Schwann cells invasion. Sixty Wistar rats were divided into four different groups receiving 10 microlitres of 0.1% EB or 0.9% saline solution into the cisterna pontis and treated or not with the xanthine. PPF treatment was done using 12.5 mg/kg/day by the intraperitonial route for 31 days of the experimental period. The rats were euthanized from 7 to 31 days after EB injection and brainstem sections were collected and processed for light and transmission electron microscopy studies. Results from both groups were compared by using a semi-quantitative method developed for documenting in semithin sections the extent and nature of remyelination of demyelinating lesions. Results showed that PPF administration after EB injection significantly increased both oligodendroglial and Schwann cell remyelination at 31 days (mean remyelination scores of 3.67 ± 0.5 for oligodendrocytes and 1.27 ± 0.49 for Schwann cells) compared to untreated animals (scores of 3.19 ± 0.57 and 0.90 ± 0.33, respectively). Microsc. Res. Tech. 77:23–30, 2014. © 2013 Wiley Periodicals, Inc.