In this study, we examined the effect of intracerebroventricular (ICV) injection of 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, or compound C (CC), an AMPK inhibitor, on the activity of sympathetic nerves innervating the adrenal gland and kidney in urethane-anesthetized rats to elucidate the role of AMPK in sympathetic nervous system function. We found that an ICV injection of AICAR or CC significantly stimulated renal sympathetic nerve activity (RSNA) and adrenal sympathetic nerve activity (ASNA) in a dose-dependent manner. Following this, we examined the role of AMPK on the sympatho-excitation caused by leptin injection. Pretreatment with AICAR or CC eliminated the leptin-induced increase in RSNA, however, neither pretreatment with AICAR or CC affected the leptin-induced increase in ASNA. Our data suggest that AMPK may regulate the sympathetic nerve system, and that the stimulating effect of leptin on sympathetic nerve activity in kidney may depend on central AMPK.