The present study was designed to evaluate whether treatment with quercetin exerts any beneficial effect on cadmium (Cd)-induced hepatotoxicity in order to establish the possible protective mechanisms of quercetin. Wistar rats were distributed in four experimental groups: control, Cd, quercetin, and Cd+quercetin. Hepatic toxicity was evaluated by measuring plasma concentrations of markers of hepatic injury. The activity of antioxidant enzymes in liver was also measured. Hepatic expression of metallothioneins (MT), and endothelial nitric oxide synthase (eNOS) was assayed by Western and Northern blot. Our results demonstrated that Cd administration induced an increased marker enzyme activity in plasma. This effect was not inhibited by quercetin. However, the administration of quercetin softened Cd-induced oxidative damage. MT levels in liver were substantially increased when the animals received Cd and quercetin. Hepatic eNOS expression was significantly increased after treatment with Cd and quercetin, being this increase higher than in animals receiving Cd alone. In conclusion, in this experimental model, quercetin was not able to prevent the Cd-induced liver damage although the animals that received both, Cd and quercetin showed a marked improvement in oxidative stress and an increase in the MT and eNOS expression. These results suggest that other mechanisms different to oxidative stress could be involved in hepatic damage.