Ghrelin, a stomach-derived hormone which induces growth hormone release and promotes positive energy balance, has been reported to inhibit cell apoptosis in endotheliocytes, osteoblasts and cardiocytes. Recent evidence has shown that ghrelin can also inhibit neuronal apoptosis of the hypothalamus and the hippocampus. However, little is known about the effects of ghrelin on the substantia nigra pars compacta (SNpc) neurons in which ghrelin's receptor, growth hormone secretagogue receptor (GHSR)-1a, is highly expressed. In the present study, we investigated whether ghrelin could protect nigral dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. We observed that ghrelin, acting through GHS-R 1a, inhibited MPTP-induced dopaminergic neuronal loss in the SNpc as well as dopamine depletion in the striatum. Ghrelin could also reverse the down-regulated the expression of Bcl-2, up-regulated the expression of Bax, and caspase-3 activation caused by MPTP. This study demonstrated that ghrelin might be a potential protector of dopaminergic neurons in a therapeutic strategy for Parkinson's disease.