Glucose-regulated protein 75 (Grp75) is an important molecular chaperone that belongs to the heat shock protein 70 family and resides predominantly in mitochondria. Grp75 can protect cells from glucose deprivation (GD) injury.However, the molecular mechanisms by which it carries out this function are unknown. Here we report that Grp75 could delay the release of cytochrome c and reduce apoptosis induced by GD, and we also found that Grp75 could decrease Bax/Bcl-2 gene expression ratio and inhibit the conformational change of Bax during this process. In conclusion, these findings suggested that Grp75 overexpression was able to inhibit apoptosis induced by GD. Grp75 inhibited Bax conformational change to delay the release of cytochrome c,thus providing protection to PC12 cell which was used primarily as a neuron model against GD toxicity.