Emerging evidence indicate the modulating effects of estrogen on dopaminergic neurons in the substantia nigra pars compacta (SNpc). One of the mechanisms underlying the effect of estrogen is through neuroglia. To determine whether estrogen affects the number of dopaminergic neurons and reactive astrocytes and microglia in the SNpc of male mice, 14-week-old C57Bl/6 male mice were injected with 17beta-estradiol (E2) or vehicle for 10.5 days. On day 11 all mice were killed and the SNpc were collected and processed for lectin (GSI-B4) histochemistry, tyrosine hydroxylase (TH) immunohistochemistry or glial fibrillary acidic protein (GFAP) immunohistochemistry. Quantitative studies demonstrated that E2 significantly increases the number of TH-immunoreactive (IR) neurons in the SNpc but the hormone induces no change either in cell number or cell morphology of GFAP-IR astroglia and GSI-B4(+ve) microglia. These observations suggest that E2 can influence the number of nigral dopaminergic neurons of male mice and possibly protects dopaminergic neuronal loss during normal aging and in Parkinson's disease.