Abstract: The purpose of this prospective study was to investigate the toxic effects of fluoride on bone tissues by assessing the serum and bone biochemical parameters in the experimental rats orally treated with 25 mg L-1 fluoride/rat/day for 8 and 16 weeks, respectively. The electron microscopic studies of bone in fluoride intoxicated rats shows flattened bone cells with damaged nucleus, endoplasmic reticulum and enlarged lacunae. An increase in serum fluoride, alkaline and acid phosphatase, sodium, potassium, phosphorous, urea, creatinine, uric acid, blood glucose levels and decrease in the levels of protein and calcium were observed in experimental groups of rats. The levels of fluoride, tartrate resistance acid phosphatase and hyaluronic acid were increased and the levels of alkaline phosphatase, collagen, chondroitin sulphate and heparan sulphate were decreased in the bone tissue of experimental groups of rats. The altered serum and bone biochemical parameters may be attributed to bone damage which in turn may leads to skeletal fluorosis.