Vitamin C is a natural nutrient with antioxidant properties and is used as a health supplement. In this study, we examined the effects of intraperitoneal administration of high-dose vitamin C (4 g/kg) on dextran sodium sulfate (DSS)-induced ulcerative colitis. We prepared a mouse ulcerative colitis model by administering DSS for 7 d along with high-dose vitamin C each day during DSS treatment. Ulcerative colitis induced by DSS was ameliorated by high-dose vitamin C administration. Blood levels of interleukin-6, tumor necrosis factor-α, hydrogen peroxide (H₂O₂), and iron were elevated in DSS-treated mice but lowered by high-dose vitamin C administration. Contrarily, the levels of H₂O₂ and iron and the numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells in the colon were further increased by high-dose vitamin C administration. The expression levels of fibroblasts, collagen type I, and collagen type III decreased in the DSS-treated mice but increased in mice administered high-dose vitamin C. These results suggest that high-dose vitamin C administration can improve ulcerative colitis.