Oxidative stress has been pointed as an important molecular mechanism for kidney injury in mercury (Hg) poisoning. Lycopene, a plentiful carotenoid in tomatoes, has been studied because of its large antioxidant properties. Here, we examined the possible in vivo protective effect of lycopene against the pro-oxidative effects of Hg in kidneys from adult rats. Rats were injected with HgCl₂ (0 or 5mg/kg B.W., sc) 6 h after lycopene had been administered (0, 10, 25 or 50 mg/kg, by gavage). After 12h, the animals were killed and kidneys were removed for analyses of antioxidants enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) using spectrophotometric methods. GPx and CAT activities were enhanced in mercury treated rats when compared to control (18.5±1.4 vs. 6.2±1.2 nmol NADPH/min/mg protein and 8.9±0.83 vs. 4.5±0.48 mg H₂O_2//min/mg protein, respectively) and this increase was prevented by all lycopene doses 10-50 mg/Kg (average values of lycopene + Hg groups: 7.78±1.49 nmol NADPH/min/mg protein and 2.86±0.41 mg H₂O_2//min/mg protein, respectively). However, SOD activity was depressed in mercury-treated rats (12.6±1.7 vs. 6.9±0.18 U/mg protein) and this decrease was prevented by all lycopene doses 10-50 mg/Kg too (average values of lycopene + Hg groups: 10.29±0.89 U/mg protein). These results suggest that SOD inhibition has been attributed to a direct interaction with mercury, while the increase of CAT and GPx activities is probably related to a defense response against reactive oxygen species generated by mercury. The lycopene administration was effective in protecting the renal antioxidant system from mercuric chloride-induced changes, suggesting that lycopene supplementation could prevent possible intoxications.