Fructose intake from added sugars correlates with the epidemic rise in obesity, metabolic syndrome and cardiovascular diseases. Fructose intake also causes features of metabolic syndrome in laboratory animals. Therefore, we have investigated whether fructose modifies lipidemia in pregnant rats and produces changes in their fetuses. Thus, fructose administration (10% wt/vol) in the drinking water of rats throughout gestation, leads to maternal hypertriglyceridemia. This change was not observed in glucose-fed rats, although both carbohydrates produced similar changes in liver triglycerides and in the expression of transcription factors and enzymes involved in lipogenesis. After fasting overnight, mothers fed carbohydrates were found to be hyperleptinemic. However, after a bolus of glucose, leptinemia in fructose-fed mothers showed no-response, whereas it increased in parallel in glucose-fed and control mothers. Fetuses from fructose-fed mothers showed hypotriglyceridemia and a higher hepatic triglyceride content than fetuses from control or glucose-fed mothers. A higher expression of genes related to lipogenesis and a lower expression of fatty acid catabolism genes were also found in fetuses from fructose-fed mothers. Moreover, although hyperleptinemic, these fetuses exhibited increased tyrosine phosphorylation of the signal transducer and activator of transcription-3 (STAT-3) protein, without a parallel increase in the serine phosphorylation of STAT-3 nor in the suppressor of cytokine signaling-3 (SOCS-3) protein levels whose expression is regulated by leptin through STAT-3 activation. Thus, fructose intake during gestation provoked a diminished maternal leptin-response to fasting and re-feeding, and an impairment in the transduction of the leptin signal in the fetuses which could be responsible for their hepatic steatosis.