The “sex-hormone” estrogen-17β promotes several cognitive functions and is a master regulator of brain bioenergetics via the estrogen receptors α and β (ERα and ERβ). In this work, by using Real-Time PCR analysis, we evaluated the effect of aging and high fat diet (HFD) on ERα and ERβ expression in rat hippocampus and cortex. In young rats, ERβ is abundant in cortex and ERα in hippocampus. During the aging, in the cortex, we observe a general decrease in ERα and ERβ expression; in hippocampus ERα increases and ERβ decreases. ER expression patterns in rat brain are also affected by the administration of an HFD. In cortex, after 4weeks of HFD, ERβ transcripts are down-regulated, whereas ERα levels remain unchanged; after 12weeks, both ERα and ERβ expression is up-regulated. In the hippocampus, the level of ERβ transcripts does not change following HDF, whereas ERα expression is affected by HDF, in a time-dependent manner: it increases after the 4-week treatment and decreases after 12weeks. Possible involvements of these receptors in the control of cortex and hippocampus functions during aging and in the modulation of energetic metabolism and feeding behaviour are discussed.