Magnesium (Mg(2+)) plays an important role in the neural system, and yet scarcely any research has quantitatively analyzed the link between endogenous Mg(2+) level and memory. Using our original technique, we measured erythrocyte intracellular ionized Mg(2+) concentration (RBC [Mg(2+)]i), which linearly correlated to recognition and spatial memory in normal aging rats. In the brain, RBC [Mg(2+)]i significantly correlated to hippocampus extracellular fluid Mg(2+) concentration, and further correlated to hippocampal synapse density. Elevation of Mg(2+) intake in aged rats demonstrated an association between RBC [Mg(2+)]i increase and memory recovery. The therapeutic effect of Mg(2+) administration was inversely correlated to individual basal RBC [Mg(2+)]i. In summary, we provide a method to measure RBC [Mg(2+)]i, an ideal indicator of body Mg(2+) level. RBC [Mg(2+)]i represents rodent memory performance in our study, and might further serve as a potential biomarker for clinical differential diagnosis and precise treatment of Mg(2+)-deficiency-associated memory decline during aging.