Contrast media induced nephropathy (CIN) is the third leading cause for acute renal failure. Pathophysiology of CIN is poorly understood, but involves hypoxia of the outer medulla. Until today, the role of osmolality of contrast media (CM) is considered the essential feature causing CIN. Here we describe a novel, perhaps most relevant characteristic of CM regarding the pathophysiology of CIN: The rheological properties, i.e. viscosity of CM. In 122 rats, we administered CM of equivalent iodine concentrations but differing physiocochemical properties: the high‐osmolality iopromide was compared to the high‐viscosity iodixanol. In addition, the non‐iodinated substances mannitol (equivalent osmolality to iopromide) and dextran (equivalent viscosity to iodixanol) were also studied. Both types of CM transiently increased renal blood flow. The high‐osmolality agents iopromide and mannitol markedly increased urine production where as iodixanol, which caused less diuresis, significantly enhanced urine viscosity. Only the high‐viscosity agents iodixanoland dextran decreased renal medullary blood flux, erythrocyte concentration, and pO2. Moreover, iodixanol prolonged the tubuloglomerular feedback response and increased plasma creatinine levels to a greater extent than iopromide or dextran. Thus, viscosity of CM may play a significant role in CIN.