Aim of the work: This study was carried out to investigate the effect of gestational and lactational administration of sodium fluoride on the rat submandibular gland and its reversibility after fluoride withdrawal. Materials and Methods: Thirty mature female albino rats were used and allowed for mating. Then the known pregnant rats were divided into three groups. The control group (group I) and their offspring were sacrificed at the age of two months. The treated group (group II) received a daily oral dose of 40mg/kg body weight sodium fluoride dissolved in distilled water via gastric tube. Drug administration started from the gestational day 10 up to the weaning on the postnatal day 21 then their offspring were administered the drug up to the age of two months then they were sacrificed. The third group(rehabilitated group) was treated in the same regimen as the second group, but their offspring were left without treatment after the weaning on the postnatal day 21 then they were sacrificed at the age of two months. Samples of the submandibular salivary gland were taken and prepared for light and electron microscopic studies. Histomorphometric technique was done to estimate the height, diameter and volume proportion of submandibular acinar and striated duct cells. Results: Prominent changes were observed in the granular convoluted tubules (GCTs), in the acini and in the striated ducts. There was reduction in the amount of secretory granules content of the GCT of the sodium fluoride treated group. This reduction was associated with signs of degeneration and vacuolation of the cytoplasm. The GCT cells showed irregular contour of cell nuclei with clumping of the nuclear chromatin. Destruction of the mitochondria can be noticed in these cells. The acinar and striated duct cells showed degenerative changes in the form of irregular dark nuclei, variable staining and vacuolation of the cytoplasm and damaged mitochondria. Dissociation of cells from the basement membrane can be detected. On the other hand withdrawal of sodium fluoride reduced to a marked degree the structural changes induced by sodium fluoride. Conclusion: It is concluded that administration of sodium fluoride in high dose in drinking water is associated with induction of destructive effect on the structure of the submandibular salivary gland. Withdrawal of sodium fluoride exposure can lead to recovery of the toxic effects of fluoride