Background: fluoride (F) is an essential element for human being from health point of view. Its intake in high doses caused toxic effects on various organs. The liver is a target organ for F toxicity. Using natural supplements is a modern approach in treatment. Aim of the Study: this study aimed to investigate the effect of sodium fluoride (NaF) on liver tissue in adult male albino rats and also to determine whether calcium (Ca) co-treatment has an ameliorative role in reversing F toxicity or not. Material and Methods: eighteen adult albino male rats were categorized into three groups (each of six animals): Group I (Control): were given distilled water and fed balanced diet, Group II (NaF treated): were given NaF at a dose of 30 mg /kg/day and Group III (NaF and Ca treated): were received NaF (similar previous dose) and 20 mg /kg/day calcium chloride (Cacl). After six weeks, under anesthesia, the livers were rapidly delivered, dissected out carefully, prepared and examined by light and electron microscopy, biochemical, immunohistochemical, morphometric studies. Results: the results showed that F induced severe histopathological changes in the liver tissue, significantly increased apoptosis and hepatic marker enzymes as compared to the control group. The histopathological changes induced by NaF included hepatocytic vacuolization, pyknosis and necrosis, vascular dilatation and congestion, Kupffer cell proliferation and periportal inflammatory cell infiltration. The ultrastructural changes of hepatocytes included nuclear disorganization (Being heterochromatic, pyknotic nuclei or disintegrated chromatin), vague mitochondria ridges, fragmentation of the rough endoplasmic reticulum, dispersed ribosomes, disruption of hepatocytes microvilli, ill defined space of Disse, Kupffer cell activation and bile canalicular dilatation. Co-treatment with Ca failed to improve liver tissue damages induced by NaF treatment. Conclusion: results of this study suggested that NaF treatment caused severe damages to liver tissue. Ca co- administration failed to reset NaF induced hepatotoxicity. Keywords: fluoride, liver, calcium, apoptosis, Caspase-3.