Effects of aging and dietary protein on the L-arginine-nitric oxide (Arg-NO) pathway and the progress of chronic nephropathy were examined. At 6-7 months of age, 10 male Fischer 344 rats were fed a 23% protein diet until 24 or 25 months of age, and another 10 were fed a 12% protein diet until that age. Twenty male Fischer 344 rats that were fed the 23% protein diet from 6 to 8 months of age were used as a control. Urinary excretion of nitrite/nitrate (NOx) at the age of 24 months in the 23% protein group was remarkably decreased, whereas in the 12% protein group, urinary NOx remained comparable to that of the control. Histological examination revealed that chronic nephropathy was highly progressive in the 23% protein group, accompanied by lowered renal function, but these changes were obviously suppressed in the 12% protein group. These results suggest that an age-related decrease in the synthesis of NO could be associated with the progress of chronic nephropathy.