Animal models suggest that decreased renal eNOS activity in old males promotes renal injury, whereas females are protected. We aimed to explore whether aging alters glomerular arginine uptake by CAT-1, the selective arginine supplier to eNOS in rats. Arginine uptake by glomeruli from young males (3 months) was significantly higher than in young females. Old males (19 months) exhibited a significant decrease in arginine transport compared to young males, whereas no differences were observed between old and young females. CAT-1 abundance remained unchanged in all experimental groups. The abundance of PKC (CAT-1 inhibitor) was significantly augmented in young females vs. young males, old vs. young males, and in old females vs. old males. No differences in PKC content were detected between old and young females. Phosphorylated PKC was significantly increased in old rats from both genders. Tocopherol, a PKC inhibitor, produced a significant increase in arginine transport and restored NO generation in old males only. Ex vivo incubation of glomeruli from old males with PMA (PKC stimulant) significantly attenuated the effect of tocopherol on arginine uptake. In conclusion: attenuated glomerular arginine transport by CAT-1 contributes to the age dependent NO deficient state in old male rats through upregulation of PKC.. In old females glomerular arginine transport is protected from the effects of PKC by an unknown mechanism.