We explored the role of reactive oxygen species (ROS) in LPS-induced bone loss. LPS was shown to increase the concentration of ROS in osteoclast precursors. The antioxidant decreased osteoclast formation by LPS. Furthermore, the antioxidant decreased NFATc1 expression by LPS, suggesting that ROS mediates NFATc1 expression in the regulation of LPS-induced osteoclast formation. Finally, the antioxidant decreased LPS-induced RANKL mRNA expression in osteoblasts. Taken together, these data indicate that LPS mediates ROS to induce bone loss.