Early-life events can exert profound long-lasting effects on several behaviors such as fear/anxiety, sexual activity, stress responses and reproductive functions. Present study aimed to examine the effects of neonatal handling on the volume and number of cells in the hypothalamic paraventricular nucleus (pPVN, parvocellular and mPVN, magnocellular regions) and the supraoptic nucleus (SON) in female rats at 11 and 90 days of age. Moreover, in the same areas, immunohistochemistry for oxytocin (OT) and glial fibrillary acidic protein (GFAP) were analyzed in the adult animals. Daily handling during the first 10 postnatal days reduced the number of cells in the pPVN and SON at both the 11 and 90 days. Handling decreased the number of OT-positive parvocellular cells in the PVN in adult females. No significant differences were detected on the optical density (OD) of GFAP-positive cells between the handled and nonhandled adult females. The effect of handling on cell loss was observed 24 h after the 10-day handling period and persisted into adulthood, indicating a stable morphological trace. Results suggest that neonatal handling can induce plastic changes in the central nervous system.