Through producing a variety of cytotoxic factors upon activation, microglia are believed to participate in the mediation ofneurodegeneration. Intervention against microglial activation may therefore exert a neuroprotective effect. Our previous study has shown thatthe electro-acupuncture (EA) stimulation at 100Hz can protect axotomized dopaminergic neurons from degeneration. To explore theunderlying mechanism, the effects of 100 Hz EA stimulation on medial forebrain bundle (MFB) axotomy-induced microglial activation wereinvestigated. Complement receptor 3 (CR3) immunohistochemical staining revealed that 24 sessions of 100Hz EA stimulation (28 days afterMFB transection) significantly inhibited the activation of microglia in the substantia nigra pars compacta (SNpc) induced by MFBtransection. Moreover, 100 Hz EA stimulation obviously inhibited the upregulation of the levels of tumor necrosis factor (TNF)-a andinterleukin (IL)-1h mRNA in the ventral midbrains in MFB-transected rats, as revealed by reverse transcriptase polymerase chain reaction(RT-PCR). ED1 immunohistochemical staining showed that a large number of macrophages appeared in the substantia nigra (SN) 14 daysafter MFB transection. The number of macrophages decreased by 47% in the rats that received 12 sessions of EA simulation after MFBtransection. These data indicate that the neuroprotective role of 100Hz EA stimulation on dopaminergic neurons in MFB-transected rats islikely to be mediated by suppressing axotomy-induced inflammatory responses. Taken together with our previous results, this study suggeststhat the neuroprotective effect of EA on the dopaminergic neurons may stem from the collaboration of its anti-inflammatory and neurotrophicactions.D 2004 Elsevier Inc. All rights reserved.