To evaluate the antioxidant potential of Lactobacillus casei Zhang (L. casei Zhang), we use hyperlipidemic rat as a model induced by high-fat diet. And then, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels of the plasma, and SOD, MDA, GSH-Px, total antioxidant capability (T-AOC), glutamic-pyruvic transaminase (GPT) and glutamic oxalacetic transaminase (GOT) of the 10% liver homogenate were determined. Except normal and hyperlipidemic control, normal prevention group (2 × 109 CFU/d of L. casei Zhang for oral administration) and three different doses of therapeutic groups (2.0 × 108, 2.0 × 109 and 2.0 × 1010 CFU/d of L. casei Zhang, respectively) were involved. Results analysis revealed that normal prevention group showed a non-significant effect on various antioxidant indexes. For therapeutic groups, supplementation of L. casei Zhang significantly decreased MDA levels (P < 0.01), whereas SOD (P < 0.05) and GSH-Px (P < 0.01) significantly increased both in serum and liver of hyperlipidemic rats. Hepatic activities of GPT and GOT were obviously reduced (P < 0.01), while T-AOC (P < 0.01) was obviously promoted by L. casei Zhang. Especially, some antioxidant indexes could recover to normal level. Antioxidative effect of L. casei Zhang was more effective for hyperlipidemic rat than normal rat. In addition, application of different therapeutic doses had variant effects on hyperlipidemic rats, and most indexes were slight except liver GSH-Px activities. It is suggested that L. casei Zhang might help to alleviate oxidative stress, as they appeared to reduce lipid peroxidation and improved lipid metabolism both in blood and liver with hyperlipidemic in vivo.