Hypoxic-ischemic brain damage has significant mortality and morbidity in newborns. Although the role of magnesium in neonatal hypoxic-ischemic brain injury related to N-methyl-D-aspartate receptors has been widely studied; the effects of magnesium on neuronal apoptosis have not been known exactly in hypoxia-ischemia. The aim of this study was to investigate the effects of magnesium on neuronal apoptosis in the 7-day-old rat hypoxia-ischemia model. Seven-day-old rats were administered magnesium sulfate (group 1; n=9) or saline (group 2; n=9) intraperitoneally before hypoxia-ischemia. Additionally 18 seven-day-old rats were given magnesium sulfate (group 3; n=9) or saline (group 4; n=9) after hypoxic-ischemic insult. Neuronal apoptosis was investigated by the dUDP-biotin nick end-labeling (TUNEL) method following 3-day recovery in all subjects. In evaluating TUNEL-positive cells, we firstly calculated the areas (mm(2)) of brain regions, hippocampus, striatum, cortex, in right and left hemispheres in subjects by IMAGE analysis. The numerical density was calculated as the number of cells per square millimeter by counting all TUNEL-positive cells. Afterwards, the ratio of right side numeric density to sum of right and left side numeric densities (right Apoptosis Index) was calculated for every brain region in rats receiving magnesium and compared to vehicle groups. The right Apoptosis Index of the hippocampus in magnesium pre-treated rats (mean+/-S.D.; 36.6+/-22.1) was significantly lower than vehicle (61.0+/-16.0; P<0.05); whereas right apoptosis indices were not changed by magnesium pre-treatment in striatum and cortex. Additionally, magnesium sulfate administration following hypoxic-ischemic insult also had no effect on right apoptosis indices in all three brain regions. It is concluded that magnesium might have a role in preventing neuronal apoptosis due to neonatal hypoxic-ischemic brain injury.