Activation of microglia is a critical pathological marker of Parkinson's disease. Activated microglia produces proinflammatory and neurotoxic factors, which cause neurons to induce neurodegeneration. Although it is believed that Chinese herbs, such as Tripterygium wilfordii Hook F, can ease inflammatory diseases, little is known about its benefit to neurodegenerative disease, like Parkinson's disease. In this study, we report the extract of Tripterygium wilfordii Hook F with a novel extraction method significantly protected dopaminergic neurons from LPS-induced degeneration in rat mesencephalic neuron-glia cultures. Cells pretreated with the extract have shown dose-dependent inhibition of LPS-induced TNFalpha and excessive NO production. More importantly, the total number of activated microglia was greatly reduced in these pretreated cells. Our results suggest that the extract of Tripterygium wilfordii Hook F has a strong bioactive function to diminish the pro-inflammatory factors, such as TNFalpha and NO. These data might also shed light for future neurodegenerative disease therapy.