Parkinson's disease (PD) is a progressive neurodegenerative disease. alpha-Synuclein (alpha-syn) oligomers play a critical role in the progression of PD. Baicalein, a typical flavonoid compound, can inhibit the formation of the alpha-syn oligomers, and disaggregate existing alpha-syn oligomers in vitro. However, whether baicalein could inhibit or disaggregate alpha-syn oligomers in vivo has not been investigated. Therefore, this study was designed to investigate the inhibitory effects of baicalein on alpha-syn oligomers in vivo and to explore the possible mechanisms of such inhibition. A chronic PD mouse model was created by continuous intragastric administration of rotenone (5 mg/kg, 12 weeks). Baicalein (100 mg/kg) was intraperitoneally injected from 7 week to 12 week. Our result showed that the amount of a-syn, changes in the levels of the striatal neurotransmitters, and the behavioral changes found in the chronic PD mouse model were prevented after the baicalein injections. Although baicalein did not decrease alpha-syn mRNA expression, alpha-syn oligomers were significantly decreased in the ileum, thoracic spinal cord, and midbrain. Furthermore, transmission electron microscopy analysis showed that baicalein could prevent alpha-syn monomers from the oligomer formation in vitro. Taken together, these results suggest that baicalein could prevent the progression of a-syn accumulation in PD mouse model partly by inhibiting formation of the a-syn oligomers. (C) 2016 Elsevier B.V. All rights reserved.