BACKGROUND: Egypt is one of the top 21 countries having problems with endemic fluorosis. High fluoride permeability allows F ion to penetrate cell membranes and accumulates in diverse soft tissues. Although fluorosis has been investigated for many years, there are relatively few studies of its effect on the digestive system such as the pancreas. The relationship between fluoride and immunity is an ongoing topic of discussion as fluoride impairs the immune system's functions. Curcumin is known to have anti-inflammatory, antioxidant, and immunomodulatory effects. OBJECTIVES: This work aimed to study the subacute toxicity of Sodium Fluoride (NaF) on the pancreas, immunity, oxidative stress, and the probable ameliorative effect of curcumin. Material and methods: the study was conducted on 60 mature male albino rats, they were randomly divided into: Group I (Negative control), Group II (Curcumin group): Rats received curcumin (15.75 mg/kg) by oral gavage daily, Group III: rats daily received NaF (10 mg /kg) by oral gavage, group IV: rats received NaF (10mg/kg/day) by oral tube concomitantly with curcumin (15.75mg/kg) daily, Group V: Rats daily received NaF (25mg /kg) by oral gavage, and Group VI: Rats received NaF (25mg/kg) by oral gavage concomitantly with curcumin (15.75 mg/kg) daily. The study was carried out for four weeks. In the end, all rats were sacrificed and blood was collected to assess the measurements of insulin, glucose, Immunoglobulin M, Immunoglobulin G, Malonodialdheyde (MDA) and total antioxidant capacity TAC levels. The pancreas was preserved for histopathological examination by light microscope. Results: The present study revealed a statistically significant decrease (P<0.001) in the insulin, IgG, IgM, and TAC levels associated with a statistically significant increase (P<0.001) in glucose , and MDA levels in NaF only treated groups. On the other hand, there were statistically significant increases (P<0.001) in the insulin, IgG, IgM and TAC levels associated with significantly significant decreases (P<0.001) in glucose and MDA levels in curcumin treated groups. The pancreatic tissue showed marked histological changes with apparent improvement with curcumin. CONCLUSION: NaF has toxic effects on pancreatic parameters, immunity, and oxidative stress. Curcumin has a protective role against such harmful effects.