Objective To study the effect of sodium fluoride on the pathological and morphological changes infemur, liver, kidney, and brain tissues of rats with fluorosis. Methods Ten healthy male and ten healthy female weanedSprague-Dawley rats were randomly divided into a control group and fluorosis group. Rats in the fluorosis group were fedwith tap water containing a fluorine ion concentration of 100 mg/ L for 12 weeks. Contents of fluoride ion in the femur,liver, kidney, and brain tissues of rats in each group were determined, as well the content of malondialdehyde (MDA) inserum, liver, kidney, and brain. Pathological and morphological changes in the femur, liver, kidney, and brain of ratswith fluorosis were observed using light microscopy and transmission electron microscopy (TEM). Results Body weight,body length, and tail length of rats in the fluorosis group were slightly lower than those in the control group, but theincidence of dental fluorosis in rats treated with fluoride was 100%. Fluoride levels in the femur, liver, kidney, and braintissues of fluorosis group rats were significantly increased compared with the control group ( P < 0. 01), and MDA contentin serum, liver, kidney, and brain of rats with fluorosis was higher than that of the control group ( P < 0. 01 or P < 0. 05).The results of pathological examination in rats with fluorosis revealed: 1) shortened bone trabecula, 2) wider trabecularspacing in bone tissue, 3) hepatocyte degeneration and vacuolization in liver tissue, 4) vacuolar degeneration of epithelialcells in the kidney proximal tubule, as well as mildly congestive and expanded interstitial tubules, and 5) sparselydistributed hippocampal cells exhibiting swelling and vacuolation. Under TEM, all the osteoblasts, hepatocytes, epithelialcells of the kidney proximal tubules, and neurons in rats treated with fluoride all exhibited shrinkage, chromatinmargination, and mitochondrial swelling. Conclusions Sodium fluoride can cause pathological damage in the femur, liver,kidney, and brain tissues in rats, and can induce cell apoptosis.