To investigate if nuclear factor-kappa B (NF-kappa B) p65 antisense oligonucleotides might affect the expression of NF-kappa B p65 and cytokines in lamina propria mononuclear cells(LPMC) from patients with ulcerative colitis (UC). LPMC were isolated from intestinal mucosal biopsy specimens from 3 patients with UC, and cultured with or without NF-kappa B p65 antisense oligonucleotides (5'-GGAACAGTTCGTCCTATGG-3'), missense oligonucleotides (5'-GGAACAGTTCGTCTATGG-3') and dexamethasone. NF-kappa B p65 expression was determined by western blot analysis. The expression of cytokine mRNA was studied by reversal transcription-polymerase chain reaction (RT-PCR). The cytokine levels were measured by enzyme linked immunosorbent assay. The results showed that NF-kappa B p65 antisense oligonucleotides resulted in down-regulation of NF-kappa B p65 expression, blocked the expression of IL-1 beta mRNA and IL-8 mRNA, and strikingly reduced the production of IL-1 beta and IL-8, and these effects were greater than those of dexamethasone in cultured LPMC from patients with UC(P < 0.05). Therefore, the application of NF-kappa B p65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with UC.