Herbal medicines have long been used to treat Parkinson's disease (PD). To systematically analyze the anti-parkinsonian activity of echinacoside (ECH) in a neurotoxic model of PD and provide a future basis for basic and clinical investigations, male C57BL/6 mice were randomized into blank control, PD model and ECH-administration groups. ECH significantly suppressed the dopaminergic neuron loss (P<0.01) caused by MPTP and maintained dopamine content (P<0.01) and dopamine metabolite content (P<0.05) compared with that measured in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage. Additionally, ECH inhibited the activation of microglia and astrocytes in the substantia nigra, which suggested the involvement of neuroinflammation. The relevant cytokines were detected with a Proteome Profiler Array, which confirmed that ECH participated in the regulation of seven cytokines. Given that p38 mitogenactivated protein kinase (p38MAPK) and NF-kappaB (NF-kappa B) signals are considered to be closely related to neuroninflammation, the gene expression levels of p38MAPK and six NF-kappa B DNA-binding subunits were assessed. Western blotting analysis showed that both p38MAPK and the NF-kappa B p52 subunit were upregulated in the MPTP group and that ECH downregulated their expressions. Minocycline was administered as the positive control to inhibit neuroinflammation, and no differences were detected between the minocycline-and ECH-mediated inhibition of the p38MAPK and NF-kappa B p52 signals. In conclusion, echinacoside is a potential novel orally active compound for regulating neuroinflammation and related signals in Parkinson's disease and may provide a new prospect for clinical treatment.