Cerebellar Purkinje cells are selectively vulnerable to ischemia, although the reasons for this are not known. Moreover, an intracellular Ca 2 +/-overload induced by excitotoxicity (toxic glutamate receptor activation) is considered to be a key mediator of central neuronal loss consequent to ischemic damage. Calbindin -D28k is an intracellular calcium binding protein that is expressed in nearly all Purkinje cells of the rat cerebellum. Its major role is presumed to be associated with intracellular Ca 2 +/-buffering. In the present work, In -Situ Hybridization and Western blot methods were used to investigate the changes of calbindin -D28k and its gene expression levels in the rat cerebellum at various times after transient global ischemia. Both level of calbindin -D28k and its mRNA expression level in the cerebellum decreased after ischemic insult, whereas the number of cerebellar Purkinje cells was unaltered after ischemia. In the light of our finding of lower levels of calbindin -D28k and its mRNA in the cerebellum, altered intracellular calcium buffering capacity in the cerebellar Purkinje cell might be presumed. It is believed that this may lead to calcium - mediated cytotoxic events after ischemic insults in cerebellum.