Abstract: Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic (DA) neurons in the Substantia Nigra pars Compacta (SNc). There is no satisfactory therapeutic strategy for PD as yet. Here, triptolide (T10), a major active compound extracted from Tripterygium wilfordii Hook. f. (TWHF), a Traditional Chinese Medicine (TCM) used to treat autoimmune diseases, was found to significantly diminish the number of abnormal rotations induced by apomorphine in 6-hydroxydopamine (6-OHDA)-lesioned PD rat model and protected DA neurons in SNc from 6-OHDA toxicity. Triptolide treatment was found to significantly suppress the activation of microglia and reduce the levels of oxidation products of proteins and lipids in the striatonigral systems of the PD model rats. Results suggest that triptolide might be a suitable lead compound in drug discovery for PD therapy.