Zoledronic acid (ZA), a nitrogen-bearing bisphosphonate, is used to treat the hypercalcemia associated with cancer. In addition to its antiumor effects, it acts as an osteoclast inhibitor. To investigate the effects of ZA on oxidative stress and antioxidants, we studied reduced glutathione (GSH) and antioxidant gamma glutamate cysteine, including nitrite and nitrate, which are endproducts of nitric oxide (NO) as well as malondialdehyde (MDA) in rabbit liver tissue. In the study ZA (100 mu g/kg) was administered to 7 rabbits that were fed ad libitum for comparison with untreated controls. MDA was studied using Thiobarbituric acid-reactive substance reduction, NO using cadmium reduction, GSH using an enzymatic method yielding dithinitrobenzene yellow substance. We observed significantly higher MDA and NO levels in the ZA group (P < .0001), whereas GSH levels were significantly lower (P < .0001). Tissues were examined histopathologically. According to our results we find ZA induced rabbit liver oxidative stress and decreases with antioxidant levels in liver tissue. Further studies are needed to explore the safe use of this agent.