In this study we examined whether sex differences in central leptin sensitive young rats disappears in middle-aged rats. As animals age, many gain visceral fat and develop leptin resistance, making them more susceptible to inflammation. Middle-aged rats were fed low-fat (LF) or high-fat (HF) diets for 2 months and during this time were given intra-3^rd-ventricular (i3vt) leptin injections in a range of doses. Females had a dose dependent decrease in food intake (FI) in response to i3vt leptin. Males reduced FI after i3vt injection of 5.0 μg leptin but not at any other dose. There was also a higher expression of hypothalamic cytokines that are part of the inflammation cascade in males including IL6, TNFα and XBP1. Females remained sensitive to i3vt leptin and had lower hypothalamic cytokine expression than males. The female rats in both diets had visceral fat percentages similar to that of the males which may mean that age increases fat in this depot in rats. These data indicate that middle-aged rats are in a transition period in terms of hormonal sensitivity that may serve as a model to study age-associated changes. Response patterns in female rats that are cycling but have not reached persistent estrous may be suggestive for explanations of physiological changes in perimenopausal women. These findings are important because aging represents a time when health is impacted by diet, body fat distribution and estrogen levels.