Baicalein, a flavonoid obtained from the root of Chinese medicinal herb Scutellaria baicalensis, has been shown to exert a protective effect on neurons against several neuronal insults. The aim of this study was to explore the neuroprotective effect of baicalein in 6-hydroxydopamine (6-OHDA)-induced experimental parkinsonism in vitro and in vivo. In in vitro experiments, we found that baicalein (0.5, 5 μg/mL) could significantly ameliorate the 6-OHDA-induced SH-SY5Y cell apoptosis from 31.56% in the 6-OHDA group to 18.90%, 21.61% respectively, and also promote neurite outgrowth of PC12 cell. In in vivo experiments, baicalein had no effect on apomorphine (APO)-induced rotations, but it could significantly attenuate muscle tremor of 6-OHDA-lesioned rats. The burst frequency and amplitude are 13.43%, 35.18% compared to 6-OHDA group. Moreover, baicalein treatment could also increase tyrosine hydroxylase (TH)-positive neurons to 265.52% of the 6-OHDA group. The neuroprotective action of baicalein was coincident with an attenuated astroglial response within the substantia nigra. Neuroprotective effect of baicalein as demonstrated by the increasing the number of dopaminergic neurons may have been, in part, caused by anti-apoptotic, pro-differentiation and anti-inflammatory mechanisms of baicalein. Therefore, baicalein can be a promising candidate for prevention or treatment of Parkinson's disease, owing to its anti-apoptotic, pro-differentiation and anti-inflammatory action.