Leptin, the ob gene product, has an important role in the regulation of body weight. Although tamoxifen, a nonsteroidal antiestrogenic agent, is known to have estrogenic effects on fat metabolism, its influence on adipose tissue remains unknown. In the present study, the effect of tamoxifen on the concentration of leptin was investigated in ovariectomized rats treated with tamoxifen or vehicle. The dosage of tamoxifen was extrapolated from the human dosage. Food intake, adipose tissue weight, and plasma insulin were assessed at the end of the experiment. Results: Tamoxifen-treated rats showed a significant reduction of body weight gain, food intake, adipose tissue weight and leptin concentration (p < 0.001). The plasma insulin level was significantly higher after tamoxifen treatment (p = 0.01) in tamoxifen-treated rats than in control rats. We concluded that tamoxifen reduces food intake in the acute phase and a reduction of adipose tissue gain may result in reduced levels of plasma leptin in ovariectomized rats. Furthermore, rats treated with tamoxifen may be resistant to insulin action.