AbstractIncreased fructose consumption is strongly associated with metabolic syndrome (MS). This study was performed to elucidate the role of co-enzyme Q10 (CoQ) and/or rosiglitazone (Rosi) in fructose induced MS. Four groups of rats (n=8–10) were fed on fructose-enriched diet (FED) for 16weeks. One served as FED-control while the remaining groups were treated with CoQ (10mg/kg/day), Rosi (4mg/kg/day) or their combination during the last 6weeks. Another group was fed on normal laboratory chow (normal control). At the end of the experiment, blood samples were collected for estimation of markers related to MS. In addition, histological examination of liver, kidney and pancreas samples was done. Induction of the MS was associated with increased body weight gain (34%) coupled with elevated levels of blood glucose (48%), insulin (86%), insulin resistance (270%), uric acid (69%), urea (155%), creatinine (129%) and blood lipids with different degrees. Fructose-induced MS also reduced plasma catalase (62%) and glutathione peroxidase (89%) activities parallel to increased serum leptin and tumor necrosis factor-alpha (TNF-α) levels. These changes were coupled by marked histological changes in the examined tissues. Treatment with CoQ or Rosi attenuated most of MS-induced changes. Besides, the combination of both agents further reduced blood glucose, total cholesterol, triglycerides and urea levels, as well as, normalized serum levels of leptin and TNF-α. In addition, combined therapy of both agents elevated HDL-cholesterol level and glutathione peroxidase activity. In conclusion, the present study proves the benefits of co-supplementation of CoQ and Rosi in a fructose-induced model of insulin resistance.