Epidemiological studies showed that daily drinking coffee or teas decreases the risk of Parkinson's disease (PD) to 40-50%. Caffeic acid (CA) and chlorogenic acid (CGA) are coffee ingredients and exert antioxidative properties. Exposure to pesticides, such as rotenone, is an environmental factor that plays an important role in the pathogenesis of PD. In this study, we examined neuroprotective effects of CA and CGA against rotenone-induced neurodegeneration. Chronic subcutaneous injection of rotenone into C57BL/6J mice exhibited reduction of dopaminergic neurons in the substantia nigra and beta-tubulin III-positive neurons in the intestinal myenteric plexus. Daily oral administrations of CA or CGA inhibited rotenone-induced cell death of not only nigral dopaminergic neurons but also myenteric plexus. In addition, CA or CGA significantly increased expression of antioxidative molecule metallothionein in the striatal astrocytes. In coculture of neurons and astrocytes from the mesencephalon or intestine, CA and CGA inhibited rotenone-induced neuronal loss of mesencephalic dopaminergic and enteric neurons, respectively. These results suggest that daily intake of coffee ingredients prevents or delays the onset of PD.