Background: Metabolic syndrome (MetS) has been recognized as a leading cause of various health complications, affecting many organs including the kidneys. The aim of the current study was to investigate the effect of pentoxifylline (PTX) on the renal dysfunction which is associated with MetS.Methods: MetS was induced in male Wistar rats by adding 10% fructose to their drinking water, as well as placing the animals on a high fat salt diet for 12 weeks. Pentoxifylline was then administered (30 mg.kg-1.day-1) orally starting from the 9th week for a duration of 4 weeks. Results: Despite having no significant effect the developed hyperinsulinemia associated with MetS, pentoxyfylline administration in the last four weeks alleviated the proteinuria associated with fructose, fat and salt (12 weeks)-induced MetS in rats. In order to investigate the mechanism of action of pentoxifylline, its effects on inflammatory mediators and enzymes was explored. Pentoxifylline significantly decreased urine 8-isoprostane levels as well as the kidney inducible nitric oxide synthase (iNOS) levels in MetS animals. An investigation of kidney glutathione reductase enzyme revealed a significantly decreased activity in MetS animals treated with pentoxifylline compared with untreated MetS rats. Pentoxifylline had no effect on the elevated kidney glutathione peroxidase found in MetS group. Conclusion: The short-term administration of pentoxifylline in rats with MetS, was found to ameliorate proteinuria and the low grade inflammation which are associated with MetS.