Vasoactive eicosanoids may be involved in glomerular hyperfiltration following a high protein intake or removal of renal mass. We sequentially measured glomerular filtration rate (GFR), proteinuria (UpV), and urinary eicosanoid excretion in sham-operated (2K) and uninephrectomized (NX) rats on two diets. Compared with 12% protein (LP), 36% protein (HP) initially resulted in a higher GFR and UpV in both 2K and NX rats. Urinary excretion of 6kPGF1alpha and TxB2 was higher on the HP diet. Ten weeks after NX, PGE2 excretion was slightly reduced, while that of TxB2 and 6kPgF1alpha was the same as in 2K rats, indicating that the excretion per kidney had increased. From week 40, the GFR of NX rats on the HP decreased, preceded by a progressive increase in UpV. Excretion of PgE2, TxB2, and 6kPgF1alpha was highest in the phase of proteinuric chronic renal failure. Thus, vasoactive eicosanoids are involved to maintain hyperfiltration induced by high protein intake or NX.