Abstract: Objective: Incidence of metabolic syndrome (MS) is strongly associated with increased fructose consumption. This study aimed to elucidate the role of pioglitazone (Pio), caffeic acid (CA) and their combination on fructose-induced MS. Materials and methods: Seven groups of rats (n=8) were used. Groups 1-3 were fed on normal diet and received 1% Tween 80 (normal control), Pio (2.7 mg/kg) and CA (20 mg/kg), respectively. Groups 4-7 were fed on fructose-enriched diet (FED) for 15 weeks. The 4th group served as positive control group, and the remaining groups received Pio, CA and their combination, respectively. Treatments started 10 weeks after the beginning of fructose feeding. At the end of the study, blood samples were collected for estimation of MS related markers.