Activation of transcription factor Nrf2 was investigated in the isolated perfused rat liver infused with 0.5 mg of colloidal carbon (CC)/ml for 5–15 min to stimulated Kupffer cell function. Infusion of CC enhanced liver O2 consumption over basal levels, with a time-dependent increase in CC-induced O2 uptake, at constant rates of CC phagocytosis by Kupffer cells, as assessed histologically, and adequate viability conditions of the livers, as shown by the marginal (0.34 %) total sinusoidal lactate dehydrogenase (LDH) efflux over intrahepatic LDH activity. Under these conditions, cytosolic protein levels of Nrf2 (Western blot) and inhibitor of Nrf2 Keap1 progressively declined by CC infusion, those of nuclear Nrf2 increased, leading to enhancement in the nuclear/cytosolic Nrf2 ratios. It is concluded that the respiratory burst of CC-stimulated Kupffer cells triggers Nrf2 activation in the perfused liver, a response that may afford cellular protection under prooxidant conditions underlying Kupffer cell stimulation.