The mechanisms of wound healing in the gut are poorly understood but are mediated by cytokines in other tissues. In this study we wanted to determine which cytokines were expressed after nonspecific colonic injury, the kinetics of that expression, and how cytokine expression correlated with tissue histology. At 0, 4, 8, 12, 24, 48, and 72 h after intrarectal administration of 3% acetic acid to C3H/HeJ mice, their colons were removed for histology, organ culture, and RNA extraction. Cytokine mRNA expression for various cytokines was assessed by reverse transcriptase-polymerase chain reaction with primers specific for each cytokine. Cytokine production in organ cultures was measured with bioassays. Shortly after colonic injury and during colonic regeneration, proinflammatory cytokines such as interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein (MIP), and transforming growth factor-beta (TGF-beta) were expressed. In contrast, expression of T cell-derived cytokines was not detected at any time point. Cytokines such as IL-1 beta, IL-6, IL-10, TNF-alpha, and MIP-1 are important mediators of tissue repair and restitution after nonspecific colonic injury and may subserve a similar role in human colitis.