In this study we measured simultaneously and sequentially the lumbar sympathetic nerve activity (LSNA) or renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) in response to insulin with co-existing hypoglycemia or with glucose replacement in normal rats. Sinoaortic denervation (SAD) was used to evaluate the influence of the baroreflex. LSNA, RSNA, MAP and HR were determined using an acquisition processor and computer software. Bolus insulin infusion where the blood glucose was allowed to decrease resulted in an immediate decrease in MAP. The HR decreased for approximately 15 min and subsequently increased. The LSNA increased immediately after insulin infusion peaking at 25 minutes and then recovered toward baseline. Insulin infusion with glucose replacement resulted in a decrease in MAP and HR. The LSNA progressively increased and was maintained throughout the experimental period. Insulin infusion with hypoglycemia increased RSNA and when hypoglycemia was prevented the RSNA decreased. SAD attenuated the decrease in MAP and LSNA response to insulin. Thus, insulin acts to decrease MAP while simultaneously increasing HR, LSNA and RSNA when hypoglycemia is allowed to occur. However, insulin acts to decrease HR and RSNA when euglycemia is maintained. The insulin-induced increase in LSNA is modulated by the baroreflex mechanism. We conclude that insulin has independent direct and indirect effects on LSNA, RSNA, MAP and HR that are modulated by glycemia and the baroreflex.