AbstractMagnesium (Mg²⁺) plays an important role in the neural system, and yet scarcely any research has quantitatively analyzed the link between endogenous Mg²⁺ level and memory. Using our original technique, we measured erythrocyte intracellular ionized Mg²⁺ concentration (RBC [Mg²⁺]_i), which linearly correlated to recognition and spatial memory in normal aging rats. In the brain, RBC [Mg²⁺]_i significantly correlated to hippocampus extracellular fluid Mg²⁺ concentration, and further correlated to hippocampal synapse density. Elevation of Mg²⁺ intake in aged rats demonstrated an association between RBC [Mg²⁺]_i increase and memory recovery. The therapeutic effect of Mg²⁺ administration was inversely correlated to individual basal RBC [Mg²⁺]_i. In summary, we provide a method to measure RBC [Mg²⁺]_i, an ideal indicator of body Mg²⁺ level. RBC [Mg²⁺]_i represents rodent memory performance in our study, and might further serve as a potential biomarker for clinical differential diagnosis and precise treatment of Mg²⁺-deficiency-associated memory decline during aging.