High concentration of corticosterone (Cort) 0.2 mM was incubated with PC12 cells to simulate the lesion state of brain neurons in depressive illness, it was found that the inulin-type oligosaccharides extracted from Morinda officinalis, inulin-type hexasaccharide (IHS) at the doses of 0.625, 1.25 μM or desipramine (DIM) 0.25, 1 μM protected the PC12 cells from the lesion induced by Cort. With Fura-2/AM labeling assay, DIM 0.25, 1 μM or IHS 2.5, 10 μM attenuated the intracellular Ca 2 + overloading induced by Cort 0.1 mM for 48 h in PC12 cells. Using RT-PCR, treatment with Cort 0.1 mM for 48 h decreased the nerve growth factor (NGF) mRNA level in PC12 cells, IHS 5, 10 μM reversed this change. In summary, IHS attenuate the intracellular Ca 2 + overloading and thereby up-regulate the NGF mRNA expression in Cort-treated PC12 cells, which may be consisted at least part of the cytopretective effect of IHS. These results also extend evidence for our hypothesis that neuroprotective action is one of the common mechanisms for antidepressants.