Epicatechin (EPI) is a dietary flavonoid that is present in many foods and possesses various bioactivities. We assessed the effects of EPI supplementation on intestinal barrier integrity in mice. Thirty-six mice were assigned to three groups and fed a standard diet or a standard diet supplemented with 50 or 100 mg EPI/kg ( = 12 per group). After 21 days of rearing, blood and intestinal samples were collected from eight randomly selected mice. Supplementation with 50 and 100 mg/kg EPI decreased ( < 0.05) the serum diamine oxidase activity and -lactic acid concentration and increased ( < 0.05) the duodenal, jejunal, and ileal abundance of tight junction proteins, such as occludin. Moreover, it lowered ( < 0.05) the duodenal, jejunal, and ileal tumor necrosis factor-α contents and enhanced ( < 0.05) the duodenal and jejunal catalase activities and ileal superoxide dismutase activity. Supplementation with a lower dose (50 mg/kg) decreased ( < 0.05) the ileal interleukin-1β content, whereas supplementation with a higher dose (100 mg/kg) increased ( < 0.05) the duodenal and jejunal glutathione peroxidase activities. Furthermore, supplementation with 50 and 100 mg/kg EPI decreased ( < 0.05) cell apoptosis, cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3), and cleaved caspase-9 contents in the duodenum, jejunum, and ileum. In conclusion, EPI could improve intestinal barrier integrity in mice, thereby suppressing intestinal inflammation and oxidative stress and reducing cell apoptosis.