In the present study, we compared the ability of acute peripheral 2-deoxy--glucose (2DG) treatment to induce food intake and increase immediate early gene expression in lactating versus virgin female rats. In Experiment 1, virgin and lactating rats were treated intraperitoneally with either saline or 2DG (400 mg/kg) and their food intake was compared across the next 6 h. In Experiment 2, lactating and virgin rats were given saline or 2DG, sacrificed 1 h later, and their brains were processed for Fos-like immunocytochemistry (FLI). The average number of cells expressing Fos protein within different brain regions was compared among the different groups. Statistical analyses of the data from Experiment 1 show that 2DG produces an increase in food intake in virgin rats, but not in lactating rats. These data correlate with the results from Experiment 2, where 2DG treatment resulted in an increase in FLI within the caudal ventrolateral medulla (cVLM), the paraventricular nucleus of the hypothalamus (PVN), and the supraoptic nucleus of the hypothalamus (SON) of cycling females. In lactating rats, however, 2DG failed to increase FLI in these regions. Together, these results show that the 2DG-induced food intake response is attenuated during lactation and this attenuation is reflected in the activation of neuronal groups that are thought to participate specifically in the food intake response to glucoprivation. Processes mediating this differential response are discussed in terms of the hormonal and metabolic changes that are characteristic of lactation.