Pre- and postnatal protein malnutrition (PMN) adversely affects the developing brain in numerous ways, but only a few studies have investigated specific glial parameters. This study aimed to evaluate specific glial changes of rats exposed to pre and postnatal PMN, based on glial fibrillary acidic protein (GFAP) and S100B immunocontents as well as glutamine synthetase (GS), in cerebral cortex, hippocampus, cerebellum and cerebrospinal fluid, on the 2nd, 15th and 60th postnatal days. We found increases in GFAP, S100B and GS in the cerebral cortex at birth, suggesting an astrogliosis. Hippocampus and cerebellum also exhibited this profile at birth. However, a significant interaction between age and diet in postnatal life was observed only in the S100B of the cerebral cortex. No changes in the content of GFAP and S100B and GS activity were found on the 60th postnatal day in malnourished rats. In contrast, following an increase in the levels of S100B in the cerebrospinal fluid, during the early developmental stages, levels remained elevated on the 60th postnatal day. Our data support the concept of astrogliosis at birth, induced by PMN, and involve extracellular-regulated kinase activation. Specific alterations in cerebral cortex emphasize the regional vulnerability of the brain to malnutrition; some alterations were observed only at birth (e.g. GFAP); others were observed on the 2nd and 15th post-natal days (e.g. ERK phosphorylation). Taken together, transient and persistent alterations (e.g. elevated extracellular levels of S100B) suggest some brain damage or a risk of brain diseases in rats exposed to PMN.