Abstract: Objective: Incidence of Metabolic Syndrome (MS) is strongly associated with increased fructose consumption. This study aimed to elucidate the role of rosiglitazone, Chromium Picolinate (CP) and their combination on fructose-induced MS. Materials and methods: Four groups of rats (n = 10) were fed on Fructose-enriched Diet (FED) for 16 weeks. One served as FED-control while the remaining groups were treated with rosiglitazone (4 mg kg-1 day-1), CP (80 μg kg-1 day-1) or their combination during the last 6 weeks. A fifth group was fed on normal diet (normal group). At the end, blood samples were collected for estimation MS-related markers. Results: Histological examination of livers, kidneys and pancreases from all groups was done. Induction of MS was associated with increased weight gain and insulin resistance coupled with elevated levels of blood glucose, insulin, uric acid, urea, creatinine and lipids. FED also reduced plasma catalase and glutathione peroxidase activities parallel to increased serum leptin and TNF-α levels. This was coupled with marked histological changes in the livers, kidneys and pancreases. Treatment with rosiglitazone or CP attenuated most of the changes associated with MS. Besides, combination of both agents further improved disease markers and decreased hepatocytes fibrosis. Conclusion: The present results reveal the benefits of co-supplementation of rosiglitazone and CP in MS.