Cassiae semen, a commonly consumed tea and medicinal food, has been shown to have multiple therapeutic actions related to the prevention of dementia and ischemia. In this study, we investigated the effects of extract of Cassiae semen (COE) against neurotoxicities in in vitro and in vivo Parkinson's disease (PD) models. In PC12 cells, COE attenuated the cell damage induced by 100 microM 6-hydroxydopamine (6-OHDA) stress in MTT assay, and it inhibited the overproduction of reactive oxygen species, glutathione depletion, mitochondrial membrane depolarization and caspase-3 activation at 0.1-10 microg/ml. In addition, COE showed radical scavenging activity in the DPPH and ABTS assays. In mesencephalic dopaminergic (DA) culture, COE protected DA cells against 10 microM 6-OHDA- and 10 microM 1-methyl-4-phenylpyridine-induced toxicities at 0.1-1 microg/ml. We also evaluated the effect of COE in a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the pole test, COE (50mg/kg, 15 days)+MPTP (30 mg/kg, 5 days)-treated group had decreased T-turn and T-LA which were longer in MPTP group. Moreover, COE significantly protected DA neuronal degeneration induced by MPTP in the substantia nigra and striatum of these mice. These results demonstrate that COE can prevent DA neurons against the toxicities involved in PD.