BACKGROUND AND AIMS: An ulcerative colitis rat model was established with baicalin as the treatment. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot analysis were used to determine inflammatory factor expression in interstitial cells of Cajal. RESULTS: Baicalin treatment reduced the ulcerative colitis symptoms, such as bloody diarrhea, reduction in body weight, and vomiting. Baicalin treatment decreased the serum levels of tumor necrosis factor α (TNFα), interleukin (IL)-1β, and IL-17A compared to the phosphate buffer saline (PBS) control group. Baicalin treatment protected the interstitial cells of Cajal against oxidative stress injury via improvements in superoxide dismutase (SOD) activity, modified disease activity index (mDAI), reactive oxygen species (ROS) production, catalase (CAT), glutathione (GSH), and nitric oxide (NO) level in the serum and interstitial cells of Cajal. Baicalin treatment decreased apoptosis of interstitial cells of Cajal. Baicalin treatment decreased the nuclear factor Kappa B (NF-κB)/ Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/ extracellular regulated kinase (Erk) / protein kinase B (Akt) signal pathway in interstitial cells of Cajal and NF-κB overexpression abrogated the decreased baicalin-induced inflammation and apoptosis of interstitial cells of Cajal induced. CONCLUSION: Baicalin treatment improved ulcerative colitis symptoms and decreased inflammation and apoptosis of interstitial cells of Cajal. Baicalin treatment inhibited inflammation and apoptosis of interstitial cells of Cajal by targeting the NF-κB pathway in an ulcerative colitis rat model, which may serve as a potential agent for the treatment of ulcerative colitis.