Mutations in the brain-derived neurotrophic factor (BDNF) gene are associated with human obesity and BDNF has potent inhibitory effects on eating and body weight. Little is known about the effects of energy-balance manipulations on BDNF protein in the hypothalamus, though this brain region is critical for regulation of feeding and body weight and has high levels of BDNF. Here we investigated the effects of negative and positive energy status on BDNF protein levels in the arcuate (ARC), paraventricular (PVN), and ventromedial (VMH) hypothalamic nuclei, and the ectorhinal cortex. To achieve this, mice were food deprived for forty-eight hours or fed a western diet (WD), a restricted amount of WD, or chow for six hours, forty-eight hours, one week, or three weeks. BDNF protein levels were estimated as the number of neurons in each brain region that exhibited BDNF-like immunoreactivity (LIR). Food deprivation decreased BDNF protein (and mRNA) expression in the ARC compared with fed mice (32%). In contrast, one week of WD consumption increased BDNF protein expression in the VMH as compared with chow or restricted WD feeding (40%), and unexpectedly, increased BDNF protein in the ectorhinal cortex (20%). Furthermore, of the diet conditions and durations tested, only one week of WD consumption was associated with both hyperphagia and excess weight, suggesting effects of one or both contributed to the changes in BDNF levels. The decrease in ARC BDNF may support increased feeding in food-deprived mice, whereas, the increase in the VMH may moderate overeating in WD fed mice.