Women exhibit higher lifetime prevalences of stress-related disorders than men. These disorders have been associated with changes in prefrontal cortex structure and function. Here, we examine the effects of acute inescapable stress, an animal model of behavioral depression and post-traumatic stress disorder, on plasma corticosterone (CORT) and on c-fos mRNA and brain-derived neurotrophic factor (BDNF) mRNA in regions of the prefrontal and frontal cortex in male and cycling female rats. Inescapable stress consisted of 100 1 mA tailshocks, and no-stress controls remained in their home cages. Rats were sacrificed immediately (0 min) or 60 min after termination of the stressor. CORT levels were increased at both 0 and 60 min post-stress termination relative to controls, and the increase was greater in females at both time points. c-fos mRNA expression increased at 0 min in prefrontal cortical regions, but this increase was greater in males than estrus and proestrus females. At 60 min, c-fos mRNA levels were lower than at 0 min in males but not females. No correlations between CORT and c-fos mRNA levels in prefrontal regions were observed in females in the stress groups, but significant correlations were observed in males in several prefrontal regions. BDNF mRNA expression was greater in control females than control males. Inescapable stress increased BDNF mRNA expression at 0 but not 60 min in males, but there was no effect of inescapable stress on BDNF mRNA in females. These results reveal sex differences in inescapable stress-induced gene expression that may have implications for differences in vulnerability to stress-related disorders.