Nesfatin-1, a newly discovered satiety molecule which reduces feeding behavior, has been recognized as a unique regulatory neuropeptide with its multiple roles, both central and peripheral. However, whether it had neuronal modulation effect on dopaminergic neurons is largely unknown. In the present study, using whole-cell patch clamp under current-clamp mode, we investigate the effects of nesfatin-1 on the electrical activity of rat nigral dopaminergic neurons. Nesfatin-1 could produce a resting membrane potential hyperpolarization on the majority of dopaminergic neurons tested. The spike frequency decreased by 23.13 ± 5.93 and 43.20 ± 5.56 % in 5-nM and 10-nM nesfatin-1 groups, respectively. These effects persisted in the presence of ionotropic glutamate and GABA receptor antagonists. Our study suggests that nesfatin-1 postsynaptically inhibits the electrical activity of nigral dopaminergic neurons.