Abstract: Objective: To study the preventive effect of tuna bone collagen peptides (TBCP) on dextran sulfate sodium (DSS) - induced acute ulcerative colitis in mice. Methods: The mice were randomly divided into normal group, model group and TBCP group. The mice in the normal group and model group were administered with normal saline every day, while the mice in the TBCP group were given 300 mg/kg bone collagen peptides daily. Except the normal group, the other two groups were treated with 3.5% DSS for 8 days to establish the acute ulcerative colitis model. During the whole experiment, the body weight of mice was recorded every day to evaluate the disease activity index (DAI). At the end of the experiment, the organs were collected to measure the organ indexs, and the colons was collected to measure the length. Also, colon paraffin slices were prepared and their pathological changes were observed under microscope after HE staining. Enzyme linked immunosorbent assay (ELISA) was used to detect the contents of LPS, DAO and the activities of SOD and GSH-Px in serum and colon tissue, respectively. Results: Compared with the normal group, the weight of mice in the model group decreased and DAI scores were significantly increased. The livers and spleens of mice in the model group were swollen and the thymus gland was atrophic. Meanwhile, the colon length were significantly shortened and pathological damage was serious. Compared with the model group, the levels of LPS and DAO in serum and colon tissue of mice in TBCP group were significantly decreased (P<0.01), and the activities of SOD and GSH-Px were significantly increased (P<0.01). Conclusion: The tuna bone collagen peptides could reduce the symptoms of acute ulcerative colitis, and it is speculated that tuna bone collagen peptides could play a role in the prevention of colitis by repairing intestinal injury and improve antioxidant capacity.