Aim To investigate the effect in berberine chloride (BER) on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium (DSS) solution or distilled water freely with different doses of BER (15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1) or sallcylazosulfapyridine (SASP, 520 mg·kg^-1), and solvent (0. 2 mL/10 mg Wt) once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index (DAI). Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 ( ICAM-1 ) proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.