Abstract: Objective To study the changes of Ca²⁺ concentration mediated by N-methyl-D-aspartate (NMDA) receptor in the neurons in the preoptic area/anterior hypothalamus (PO/AH) of anoxic SD rats by investigating the properties of NMDA receptor. Methods The effects of NMDA receptor agonist NMDA and antagonist vaproic acid (VPA) on the[Ca²⁺]_i in PO/AH neurons were observed in SD rats with anoxia. Results Under normal condition, the fluorescencet ratio was 0.95, which increased obviously in response to treatment with NMDA at 40 s and reached the peak value, 2.054, after 25 s with an increment of (109±52)%. After the addition of the agonist, the peak value reached 3.783 in 30 s and maintained the high level. The concentration of Ca²⁺ increased by (286±91)% after the treatment with NMDA. While in the anoxia group, the concentration of Ca²⁺ decreased by (103±45)% after the addition of VPA. Conclusions The increase in the concentration of Ca²⁺ results predominantly from the opening of NMDA receptor channel which allows Ca²⁺ influx. VPA may decrease the activity of NMDA receptor to reduce the Ca²⁺ concentration for the protection of the neurons against anoxia.