Corticotropin-releasing factor (CRF) acts to promote stress-like physiological and behavioral responses and is mainly expressed in the paraventricular hypothalamic nucleus (PVN). Urocortin 1 (Ucn1) is also a ligand to CRF type 1 and 2 receptors that has been associated with the stress response. Ucn1 neurons are primarily found in the Edinger-Westphal (EW) nucleus. It has been previously proposed that CRF and Ucn1 differently modulate stress responses to distinct types of stressors. The present study used male Wistar rats to compare the effects of acute restraint stress and unpredictable chronic stress (UCS) through Fos-immunoreactivity (Fos-ir) on CRF-containing neurons of PVN and Ucn1-containing EW centrally projecting neurons. Results showed that PVN neurons responded to both acute restraint and UCS. Also for the PVN, unspecific variables, dependent on the time animals remained in the laboratory, do not seem to alter Fos-ir, since no significant differences between acute and chronic control groups were found. On the other hand, EW neurons were only activated in response to acute restraint stress. Also, for this nucleus a significant difference was found between acute and chronic control groups, suggesting that unspecific variables, dependent on the time animals remain in the laboratory, interfere with the nucleus activation. These results suggest that CRF/Ucn1 neuronal circuits encompass two interconnected systems, which are coordinated to respond to acute stressors, but are differentially activated during chronic unpredictable stress.