Neuron/glial 2 (NG2)-expressing cells are often referred to as oligodendrocyte precursor cells. NG2-expressing cells have also been identified as multipotent progenitor cells. However, microglia-like NG2 glial cells have not been fully examined in neurodegenerative disorders such as Parkinson's disease (PD). In the present study, we chose two rat models of PD, i.e., intranigral or intrastriatal injection of 6-hydroxydopamine (6-OHDA), since the cell bodies of dopamine (DA) neurons, which form a nigrostriatal pathway, are in the substantia nigra pars compacta (SNpc) while their nerve terminals are in the striatum. In the nigral 6-OHDA-injected model, activated NG2-positive cells were detected in the SNpc but not in the striatum. In contrast, in the striatal 6-OHDA-injected model, these cells were detected in both the SNpc and the striatum. In both models, activated NG2-positive cells were located close to surviving tyrosine hydroxylase (TH)-positive neurons in the SNpc. In addition, activated NG2-positive cells in the SNpc coexpressed ionized calcium-binding adaptor molecule 1 (Iba1), a microglia/macrophage marker. Interestingly, these double-positive glial cells coexpressed glial cell line-derived neurotrophic factor (GDNF). These results suggest that microglia-like NG2 glial cells may help protect DA neurons and may lead to new therapeutic targets in PD. © 2010 Wiley-Liss, Inc.