The mechanism underlying the antiepileptic function of deep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) remains unknown, presumably related to functional lesioning of target. We measured the regional normalized cerebral metabolic rate of glucose (nCMRglc) with (18)F-fluorodeoxyglucose (FDG)-MicroPET in animals receiving either ATN stimulation or lesioning. Bilateral ATN stimulation reversibly increased glucose uptake in the target region, the thalamus and hippocampus, and decreased glucose uptake in the cingulate cortex and frontal cortex. However, bilateral ATN lesioning decreased glucose uptake only in the target region. Animals with bilateral ATN lesions showed no metabolic changes after ATN stimulation. Thus, bilateral DBS of the ATN reversibly induces metabolic activation of the target area and modulates energy metabolism in remote brain regions via efferent or afferent fibers in non-epileptic rats. DBS of the ATN may work by a different mechanism than ATN lesioning.