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Fibrosis development in ulcerative colitis is directly associated with the severity of mucosal inflammation, which increases the risk of colorectal cancer. The transforming growth factor-beta (TGF-b) signaling pathway is an important source of tissue fibrogenesis, which is directly stimulated by reactive oxygen species produced from nicotinamide adenine dinucleotide phosphate oxidases (NOX). Among members of the NOX family, NOX4 expression is up-regulated in patients with fibrostenotic CD and in dextran sulfate sodium (DSS)-induced murine colitis. The aim of this study was to determine whether NOX4 plays a role in fibrogenesis during inflammation in the colon, using a mouse model.