Oestradiol is a potent anorectic agent that reduces both food intake and body weight. Since leptin is known to reduce food intake, we first analysed if the anorectic effect of oestradiol is driven by an increased leptin concentration in either cerebrospinal fluid or plasma. Oestradiol also reduces body weight and fat mass. Accordingly, a decrease in plasma leptin concentration can also be expected after an oestradiol-driven reduction in fat mass. To test this hypothesis was the second aim of this study. Female Wistar rats received oestradiol chronically during 14 days. During the first week of treatment there was a reduction in food intake, body weight and fat mass that returned to initial values during the second week, but no changes in ob mRNA levels were found in white adipose tissue depots. There was no effect of treatment or time on plasma and cerebrospinal fluid leptin concentrations. Therefore, the anorectic effect of oestradiol is not driven by an increase in leptin concentration either in plasma or in cerebrospinal fluid, and the reduction in fat mass that oestradiol produces is not followed by a reduction leptin concentration.