Exogenous Arginine slows the progression of chronic renal failure in remnant rats through a nitric-oxide(NO)-dependent mechanism. We tested whether the inhibition of arginase could induce similar results through the increased availability of endogenous Arginine. Three Groups of remnant rats were studied for 8 weeks: 1) untreated rats (Group REM); 2) remnant rats +1% Arginine (Group ARG); 3) remnant rats administered a Mn⁺⁺-free diet, to inhibit arginase (Group MNF). Normal rats were used as controls (Group NOR). Liver arginase activity was depressed in MNF-rats (-35% vs REM, p<0.01). No difference was detected in metabolic data throughout the study among the Groups; BP was significantly lower in Group MNF vs ARG and REM after 6 weeks (p<0.001). GFR was greatly depressed in REM rats (-47% vs NOR, p<0.03), but resulted higher in Group ARG and MNF (+40 and +43% vs REM, respectively, p<0.05), with comparable changes in renal hemodynamics. Despite the better GFR, proteinuria was decreased both in Group ARG and MNF (-42%, p<0.05, and -57%, p<0.01, respectively, vs Group REM). Arginine plasma levels, significantly reduced in Group REM (-41% vs Group NOR, p<0.01), were partially restored in Group MNF (+38% vs REM), and urinary nitrite excretion, greatly depressed in Group REM (-76% vs NOR, p<0.01), were significantly increased in Group MNF (+209% vs REM, p<0.05). At renal level, arginase activity was only slightly depressed in Group MNF (-18% vs REM), but intrarenal concentrations of Arginine resulted lower in this latter Group (p<0.05 vs other Groups). Beyond the hemodynamic modifications, rats of Group MNF showed a lower glomerular sclerosis index (p<0.05 vs Group REM and ARG). Inhibition of arginase slows the progression of CRF in remnant rats similarly as in arginine-treated rats; the better histological protection in MNF-rats, however, suggests that additional factors are involved in these modifications.