The mechanism underlying the toxicity of fluoride still remains unknown. To investigate the effects of different doses of fluoride on blood and tissue oxidative stress and apoptosis, we exposed male rats to three doses of fluoride (10, 50 and 100ppm in drinking water) for a period of 10 weeks. The results suggested that exposure to 10ppm fluoride significantly increased the level of reactive oxygen species (ROS) in blood accompanied by a decrease in glutathione (GSH) level. No evidences of oxidative stress in soft tissues were seen. Fluoride (10ppm) also decreased GSH/GSSG ratio significantly. Contrary to expectation, 50 and 100ppm fluoride exposure did not produce a more pronounced toxicity in the soft tissues. However, we observed a significantly elevated concentration of ROS and depleted GSH level in blood. Exposure to fluoride did not produce any sign of apoptosis. To support our above mentioned biochemical observations and to suggest possible mechanism of action of fluoride, IR spectra of brain tissues were recorded. The results of these spectra indicated significant shift in the characteristic peak of -OH group in animals exposed to 10ppm fluoride however at higher doses, the shift was minimal. It can thus be concluded that fluoride-induced toxicity is mediated through oxidative stress particularly at a comparatively lower level of exposure however at the higher doses the mode of action still unclear and needs further investigation.