Inflammatory bowel disease (IBD) correlates with oxidative stress, inflammation, and alteration in several signal pathways, including nuclear transcription factor-kappaB (NF-κB). Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, has been widely demonstrated to exhibit an antioxidant and anti-inflammatory function. This study aimed to test the hypothesis that NF-κB inhibitor PDTC confers a beneficial role in a colitis model induced by dextran sodium sulfate (DSS) in mouse. The results showed that DSS decreased daily weight gain, induced colonic inflammation, suppressed the expression of antioxidant enzymes and tight junctions, and activated NF-κB and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathways. PDTC significantly upregulated (P < 0.05) Gpx1, Gpx4, occludin, and ZO-1 expressions in the DSS-induced colitis model. Meanwhile, PDTC reversed (P < 0.05) the activation of NF-κB signal pathway caused by DSS treatment. In conclusion, PDTC could serve as an adjuvant therapy for the patient with IBD. ©2015, Springer Science+Business Media New York.