The aim of this study was to investigate the potential protective effect of Lycium barbarum polysaccharides (LBP) pretreatment against cadmium (Cd)-induced hepatotoxicity in rats. Wistar rats were divided into control group, LBP group (300 mg/kg orally, once a day, for 30 days), Cd group (CdCl2 4 mg/kg i.p. once), and LBP + Cd group (LBP 300 mg/kg orally, once a day, for 30 days + CdCl2 4 mg/kg i.p. 24 h after the last treatment). Cd liver injury was examined by morphological/histological changes, transaminases, total protein concentration, and oxidative stress evaluated by MDA, 3NT, GSH, SOD, and TEAC activities. Cd intoxication caused gross morphological changes with hyperemia of the parenchyma, increased volume, and disappearance of the anatomical limits of the lobes associated with an increase of ALT, GSH, and TEAC in plasma and a decrease of MDA, GSH, and TEAC in liver, SOD, and total proteins in plasma. LBP pretreatment caused a slight improvement in the histological architecture and in the 3NT amount together with a significant improvement of hematic parameters. On the basis of the obtained results, we can affirm that LBP pretreatment can ameliorate liver conditions, but further studies are needed to better evaluate the protective antioxidant effects of LBP against Cd-induced toxicity.