Introduction: The spleen is a large lymphoid organ that plays an important role in immunity. Potassium dichromium is well-known to be toxic. Nanoselenium is a potent antioxidant trace mineral. The aim of the work was to explore the influence of potassium dichromate on the spleen and the co-administration of nanoselenium against the induced splenic injury. Material and methods: 30 adult male albino rats (200-250g) were equally randomly divided into three groups. Group I (the control group) received no treatment. Group II (the chromium-treated group) received potassium dichromate (2 mg/kg b.w. dispersed in 1 ml distilled water) intraperitoneally daily for 2 weeks. Group III (the chromium and selenium-treated group) received nanoselenium (0.5 mg/kg b.w. dissolved in 0.5 ml of phosphate-buffered saline, intraperitoneally) as well as potassium dichromate (2 mg/kg b.w. dispersed in 1 ml distilled water) intraperitoneally daily for 2 weeks. Then, the spleens of all groups were extracted and processed to be studied. Results: The chromium-treated group revealed disturbance of the architecture of the white pulp, congestion of the red pulp, deposition of hemosiderin pigments, chromatin condensation of the lymphocytes' nuclei, and markedly dilated rough endoplasmic reticulum of the plasma cells. There were significant increases in the area percentage of collagen fibers deposition and iron staining and a significant decrease in the area percentage of Bcl-2 immune expression. The administration of nanoselenium in Group III ameliorated most of these toxic effects. Conclusion: Nanoselenium exhibited a protective role against the toxic effect of potassium dichromate on the spleen.