Matrine is an alkaloid found in kinds of Sophora plants mainly including Sophora flavescens, Sophora alopecuroides and Sophora subprotrata. The aim of the present study was to evaluate therapeutic effects of matrine on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Two hours following colonic instillation of TNBS, matrine with several doses was given by gastric gavage once daily for 7 days. Comparing with the 0.9% NaCl-treated mice with TNBS-induced colitis, matrine (10 and 20 mg kg(-1))-treated mice with TNBS-induced colitis were shown improvements of weight loss, macroscopic score, histological score, and myeloperoxidase (MPO) activity. Moreover, treatments with matrine (10 and 20 mg kg(-1)) decreased the up-regulated mRNA and protein levels of tumour necrosis factor-alpha (TNF-alpha) caused by TNBS. Our findings suggest that matrine improves TNBS-induced colitis in mice and the therapeutic mechanism might be related to the reduction of up-regulated colonic TNF-alpha production caused by TNBS.