Arginine is a conditionally essential amino acid. To elucidate the influence of 
l-arginine on the activation of endogenous antioxidant defence, male Wistar rats 
were orally administered daily with l-arginine at different levels of 25, 50, 
100 mg/100 g body weight. After 7 and 14 days feeding, the antioxidative 
capacities and glutathione (GSH) contents in the plasma and in the liver were 
uniformly enhanced with the increasing consumption of l-arginine, whereas the 
oxidative stress was effectively suppressed by l-arginine treatment. After 14 
days feeding, the mRNA levels and protein expressions of Keap1 and Cul3 were 
gradually reduced by increasing l-arginine intake, resulting that the nuclear 
factor Nrf2 was activated. Upon activation of Nrf2, the expressions of 
antioxidant responsive element (ARE)-dependent genes and proteins (GCLC, GCLM, 
GS, GR, GST, GPx, CAT, SOD, NQO1, HO-1) were up-regulated by l-arginine feeding, 
indicating an upward trend in antioxidant capacity uniformly with the increasing 
consumption of l-arginine. The present study demonstrates that the 
supplementation of l-arginine stimulates GSH synthesis and activates Nrf2 
pathway, leading to the up-regulation of ARE-driven antioxidant expressions via 
Nrf2-Keap1 pathway. Results suggest the availability of l-arginine is a critical 
factor to suppress oxidative stress and induce an endogenous antioxidant 
response.