Oxytocin (OT), a hypothalamic neuropeptide, has been implicated in the regulation of social behaviors in rodents and humans. This study assessed the effects of intranasal administration of OT on depressive-like behaviors and hippocampal neurogenesis in adult rats following neonatal maternal deprivation (NMD). Here, we show that NMD resulted in significant depression-like behaviors, as indicated by decreases in physical activity and emotional reactivity in a novel environment, in 2-month-old animals. Notably, the OT levels in the plasma, hypothalamus, and hippocampus were decreased in these animals. Intranasal administration of OT reduced the depressive-like behaviors in NMD rats and rescued hippocampal long-term plasticity impaired by NMD stress in rats by promoting hippocampal neurogenesis. These results indicate that OT alleviates the depressive-like behaviors in NMD adult rats, probably mediated by improving adult hippocampal neurogenesis.