To study the effects of selenium and zinc on oxidative stress, apoptosis, and cell cycle changes in rat renal cells induced by fluoride. Methods Wistar rats were given distilled water containing sodium fluoride (50 mg/L NaF) and were gavaged with different doses of selenium-zinc preparation for six months. Four groups were used and each group had eight animals (four males and four females). Group one, sham-handled control; group two, 50 mg/L NaF; group three, 50 mg/L NaF with a low dose of selenium-zinc preparation (0.1 mg/kg Na2 SeO3 and 14.8 mg/kg ZnSO4·7H2O); and group four, 50 mg/L NaF with a high dose of selenium-zinc preparation (0.2 mg/kg Na2 SeO3 and 29.6 mg/kg ZnSO4·7H2O). The activities of serum glutathione peroxidase (GSH-Px), kidney superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and glutathione (GSH) in the kidney were measured to assess the oxidative stress. Kidney cell apoptosis and cell cycle were detected by flow cytometry. Results NaF at the dose of 50 mg/L increased excretion of fluoride in urine, promoted activity of urineγ-glutamyl transpeptidase (γ-GT), inhibited activity of serum GSH-PX and kidney SOD, reduce kidney GSH content, and increased kidney MDA. NaF at the dose of 50 mg/L also induced rat renal apoptosis, reduced the cell number of G2/M phase in cell cycle, and decreased DNA relative content significantly. Selenium and zinc inhibited effects of NaF on oxidative stress and apoptosis, promoted the cell number of G2/M phase in cell cycle, but failed to increase relative DNA content significantly. Conclusion Sodium fluoride administered at the dose of 50 mg/L for six months induced oxidative stress and apoptosis, and changes the cell cycle in rat renal cells. Selenium and zinc antagonize oxidative stress, apoptosis, and cell cycle changes induced by excess fluoride. To study the effects of selenium and zinc on oxidative stress, apoptosis, and cell cycle changes in rat renal cells induced by fluoride. Methods Wistar rats were given distilled water containing sodium fluoride (50 mg / L NaF) and were gavaged with different doses of Group one, sham-handled control; group two, 50 mg / L NaF; group three, 50 mg / L, selenium-zinc preparation for six months. NaF with a low dose of selenium-zinc preparation (0.1 mg / kg Na2 SeO3 and 14.8 mg / kg ZnSO4.7H2O); and group four, 50 mg / L NaF with a high dose of selenium-zinc preparation The activities of serum glutathione peroxidase (GSH-Px), and the levels of malondialdehyde (MDA) and glutathione (GSH) in the kidney were measured to assess the oxidative stress. Kidney cell apoptosis and cell cycle were detected by flow cytometry. Results NaF at the dose of activity 50 mg / L increased excretion of fluoride in urine, promoted activity of urine γ-glutamyl transpeptidase (γ-GT), inhibited activity of serum GSH-PX and kidney SOD, reduced kidney GSH content, and increased kidney MDA. of 50 mg / L also induced rat renal apoptosis, reduced the cell number of G2 / M phase in cell cycle, and decreased DNA relative content significantly. Selenium and zinc inhibited effects of NaF on oxidative stress and apoptosis, promoted the cell number of G2 / M phase in cell cycle, but failed to increase relative DNA content significantly. Conclusion Sodium fluoride administered at the dose of 50 mg / L for six months induced oxidative stress and apoptosis, and changes the cell cycle in rat renal cells. Selenium and zinc antagonize oxidative stress, apoptosis, and cell cycle changes induced by excess fluoride.