Insulin is secreted by the pancreas and plays a major role in peripheral glucose metabolism. Insulin also acts centrally within the hypothalamus to suppress appetite and regulate glucose metabolism.  During pregnancy food intake is increased and glucose metabolism undergoes marked changes to adapt to the increased demand of the fetus for glucose.  The aim of the current study was to investigate if central insulin signaling is altered during pregnancy.  Day 14 pregnant and nonpregnant rats with a surgically implanted cannula in the lateral ventricle were injected intracerebroventricularly (i.c.v.) with either insulin (10mU in saline) or vehicle (saline) and killed approximately 35 minutes later.  Brains were collected for insulin-induced phosphorylated Akt (pAkt) analysis by western blot and immunohistochemistry from two replicate groups of animals. In the arcuate nucleus and ventromedial nucleus of the hypothalamus, insulin increased pAkt in nonpregnant rats. This insulin-induced response, however, was significantly impaired in the pregnant rats.  Immunohistochemistry analysis for pAkt in the arcuate nucleus showed a decrease in the number of pAkt-positive cells following insulin treatment in pregnant rats compared to nonpregnant rats.  In the dorsomedial nucleus and paraventricular nucleus of the hypothalamus, the pAkt response to i.c.v. insulin treatment was similar in nonpregnant and pregnant rats. These data indicate that central insulin signaling is altered during pregnancy in the arcuate nucleus and the ventromedial nucleus of the hypothalamus.  This change in hypothalamic sensitivity to insulin during pregnancy may be an adaptive response that contributes to increased food intake and changes in glucose metabolism during pregnancy.