Background. Liver Growth Factor (LGF) is a mitogen for liver cells with regenerative properties in several biological systems, including the cardiovascular system. We have previously reported that short-term treatment with LGF improves vascular structure and function and lowers blood pressure in spontaneously hypertensive rats (SHR) (1), a rat model of human essential hypertension with high levels of oxidative stress. LGF is an albumin-bilirubin complex, and bilirubin and albumin-bound bilirubins are known to have antioxidant properties (2,3). We hypothesize that the antihypertensive and antifibrotic effects of LGF in SHR might be related to its antioxidant capacity. The aims of the study were: 1) to test if the production of superoxide anion is reduced in arteries and smooth muscle cells (SMC) derived from SHR rats treated with LGF (SHR-LGF); 2) to test the direct antioxidant properties of LGF on nitric oxide (NO)-mediated responses in the presence of a superoxide anion donor. Methods. Superoxide anion production was assessed by dihydoethidium (DHE) and confocal microscopy in mesenteric resistance arteries and in SMC primary cultures derived from adult male WKY, SHR and SHR treated with LGF (4.5 μg LGF/rat, i.p., twice a week during 2 weeks). Isometric tension was studied in intact carotid arteries isolated from adult male Sprague-Dawley rats. Concentration-response curves to Ach were obtained before and after 20 min pre-incubation with the superoxide anion donor pirogallol (10-6 M). Thereafter, the antioxidant effects of LGF (0.3 nM) were compared with those of the superoxide anion scavengers superoxide dismutase (SOD, 15 U/ml) and tiron (10 mM). Results. Superoxide anion production, measured by intensity of fluorescence emitted by DHE was significantly higher in SHR compared with WKY and it was reduced in SMC and arteries derived from LGF-treated SHR. Pirogallol reduced to 42% Ach-mediated relaxation. In the presence of pirogallol, the addition of LGF, SOD or tiron improved Ach relaxation to 71%, 65% and 89%, respectively. Conclusions. 1) SHR treatment with LGF reduces oxidative stress in vascular tissues; 2) LGF also has antioxidant effects on arteries “in vitro”, protecting NO from degradation by superoxide anion. These data suggest that LGF might exert its vascular protective actions in hypertension, at least in part, by reducing oxidative stress.