The key role of osteoblasts in skeletal fluorosis makes the exploration of the possible mechanisms of the fluoride-induced oxidative stress of osteoblasts of great importance. In this article, the in vitro effects of fluoride on the oxidative stress of osteoblasts are presented. To study the inhibitory effect of baicalein on the oxidative stress of osteoblasts, the antioxidant activity of baicalein was evaluated for osteoblasts exposed to fluoride. Calvarial osteoblasts were prepared and respectively treated with alpha-MEM (5% calf serum) containing 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 20.0 mg/L fluoride for 48 h. Baicalein (10 micromol/L) was added to the cells for the same period of time as that of the fluoride treatment. Low concentrations of fluoride (0.5-2 mg F-/L) stimulated the mitochondrial activity of osteoblasts and produced significant reaction to the oxidative stress, whereas high concentrations of fluoride (>or=12 mg F-/L) inhibited cell proliferation and the activity of antioxidant enzymes. This suggests that the oxidative stress induced by low concentrations of fluoride might mediate or participate in the process of fluoride inducing the proliferation of osteoblasts. The viability of osteoblasts in the high concentrations of fluoride with the addition of 10 mumol/L baicalein (>or=12 mg/L) was higher than those of the same level of fluoride- treated groups without the addition of baicalein. The protective role of baicalein is obvious as an inhibitor of lipid peroxidation against the damage induced by the high concentration of fluoride.