We evaluated the neuroprotective effects of D-psicose, one of the rare sugars, on 6-hydroxydopamine (6-OHDA)-induced apoptosis in catecholaminergic PC12 cells, the ill vitro model of Parkinson's disease (PD). Apoptotic characteristics of PC12 cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. The results showed that D-psicose at a concentration of 50 mM, exerted significant protective effects against the 6-OHDA (200 mu M)-induced PC12 cell apoptosis, while other sugars had little or no protective effects. We have observed a significant increase in the level of intracellular glutathione after 24 h in 6-OHDA (200 mu M) treated cells, while a decrease in the level was observed at 3 h and 6 h. Also, a synergistic exposure to D-psicose and 6-OHDA for 24 h showed a significant increase in intracellular glutathione level. Therefore, these results suggest that D-psicose may play a potential role as a neuroprotective agent in the treatment of neurodegenerative diseases by inducing an up-regulation of intracellular glutathione.