Abstract: AIM: To study the decreasing effects and the mechanisms of d-,-l-and dl-butylphthalide (NBP) on intracellular calcium (Ca²⁺i) in neurons subjected to hypoxia and hypoglycemia. METHODS: Neurons were prepared from fetal or newborn rat brain and Fura 2/AM was used as fluorescence indicator to study the actions of NBP on Ca²⁺i. Thapsigargin, glutamine, KCl or calcium ionpore A23187, which can induce increase of intracellular calcium, were used as tool drugs to analyze the mechanisms of the action of chiral NBP. RESULTS:d-,l- and dl-NBP were shown to significantly inhibit the increase of intracellular calcium caused by hypoxia and hypoglycemia. However, chiral NBP was found to have no effect on the increase of Ca²⁺i induced by the tool drugs except thapsigargin. d NBP seemed to have some decreasing effect on+glutamate. CONCLUSION: The actions of d-,l- and dl NBP might be mediated mainly by its decreasing effect on the release of calcium from intracellular calcium pool.