Abstract: AIM　To study the change of intracellular ［Ca²⁺］i and pH in cultured neurons after fluid percussion injury, and the therapeutic effect of drugs. METHODS　The neurons of Sprague Dawley rats were cultured for 8-14 days, then treated them with fluid percussion injury (2.5 kPa, 20 ms). Alterations of ［Ca²⁺］i and pH in single neural cell following fluid percussion injury were measured by a laser scanning confocal microscope. After being injured for several hours the cultured neurons were treated with nimodipine or D-(-)-2-amino-5-phosphonovaleric acid (D-AP-5). Two hours later, the effects of drugs on intracellular ［Ca²⁺］i and pH were studied. RESULTS　The Intracellular ［Ca²⁺］i increased quickly after brain injury and reached peak in 12 hours. It then decreased gradually and became normal at 48 hours. The pH decreased slowly, reached minimum in 12 hours, and then kept at a lower level. It did not recover normal at 48 hours. Nimodipine and D-AP-5 decreased significantly the ascension of ［Ca²⁺］i and the descent of pH. But nimodipine and D-AP-5 must be given within 10 hours after injury for a good therapeutic effect. CONCLUSION　According to the change of intracellular ［Ca²⁺］i and pH, early use of nimodipine and D-AP-5, will get a better therapeutic effect.