The potential effect of recombinant human interleukin-11 (rhIL-11) on trinitrobenzene sulfonic acid (TNB)-induced colitis was investigated in rats. Intrarectal TNB (40 mg in 0.25 ml 40% ethanol) produced significant ulcerative colitis. The lesions were most severe at three days after TNB instillation, and then declined, but lesions were still observed after two weeks. TNB administration also significantly enhanced the colonic mucosal myeloperoxidase (MPO) levels, which paralleled the severity of colitis. The rhIL-11 at subcutaneous doses of 300 or 1000 micrograms/kg daily for seven days, or 1000 micrograms/kg for three days when given after TNB significantly decreased lesion formation in TNB-induced colitis. These treatments also significantly reduced colonic mucosal MPO levels. TNB enhanced colonic mucosal levels of PGE2, LTB4, and TxB2, but these arachidonic acid derivatives were not affected by the present rhIL-11 treatments. TNB administration for three days caused a body weight loss that returned to normal after 14 days. The rhIL-11 significantly reduced colonic lesion severity and reduced colonic fecal blood loss. Given alone, rhIL-11 did not influence body weight. It can be concluded that rhIL-11 was protective against TNB-induced colitis and reactions of colonic MPO, but that these responses were not mediated through modulation of eicosanoid metabolism.