Lactic acid bacteria play an important role in the human and animal defense against liver damage. However, the potential mechanism of Lactobacillus casei (L.casei) on hepatic injury remains unclear. The objective of the present investigation was to assess the possible effect of L.casei against sodium fluoride (NaF) induced- hepatic injury in rats. Rats were allocated into three groups; first group received only distilled water thought the experiment. Second group received orally NaF (10mg/kg) for 4 weeks. Third group received NaF (10mg/kg; p.o) concurrently with L.casei (109CFU/kg.b.w.; p.o) for 4 weeks. Our study revealed that exposure to NaF increased the values of serum hepatic enzymes with increased levels of lactate dehydrgenase (LDH), nitric oxide (NO) and total bilirubin levels. In addition, NaF intoxication was associated with a reduction in the activities of glutathione (GSH) and an increment in malonaldheyde (MDA) in hepatic tissues. Moreover, a significant increment in the release of NF-κβ and caspase-3 with disturbed histopathological and ultrastructural architecture of liver cells of rats intoxicated with NaF. Conversely, L.casei supplementation (109CFU/kg.b.w.; p.o) could prevent NaF-induced hepatotoxicity, most likely as a result of possessing high antioxidant properties and anti-inflammatory activities. In conclusion, based on our findings, L.casei is effective treatment in hepatic injury and daily administration of L.casei is recommended to mitigate the deleterious effects of F-containing compounds.