The effects of Wumeiwan (WMW) on TNF-alpha, IL-6, IL-8, IL-10 and NF-kappaBp65 in rats with ulcerative colitis (UC) were investigated, the curative effectiveness of WMW vs salicylazosulfapyridine (SASP) was compared, and the action mechanism was analyzed. Fifty-Six Sprague-Dawley (SD) rats were randomly divided into four groups (n=14 in each group, with equal ratio of male and female): normal control group, model group, SASP group, and WMW group. Except normal control group, the rat UC models in the remaining three groups were established using the method of 2.4-dinitrochlorobenzene (DNCB) immunization and acetic acid local enema. The rats in model group, SASP group, and WMW group were treated with distilled water, SASP, and WMW respectively. The changes in the symptoms and signs were observed, and levels of IL-6, IL-8, TNF-alpha, IL-10 and the expression of NF-kappaBp65 in the colonic tissues were statistically analyzed. The results showed that the levels of IL-6, IL-8, and TNF-alpha were significantly increased (P<0.01), while those of IL-10 significantly reduced (P<0.01) after establishment of rat UC models as compared with normal control group. The levels of IL-6, IL-8, and TNF-alpha were obviously lower, but the level of IL-10 was obviously higher in WMW and SASP groups than those in model group (P<0.05). The levels of IL-6, IL-8, and TNF-alpha were lower, while the level of IL-10 was higher in WMW group than in SASP group. NF-kappaBp65 was expressed negatively or weakly in normal colonic tissues. The positive expression rate of NF-kappaBp65 in WMW group and SASP group was obviously lower than in model group (P<0.01), and there was significant difference between WMW group and SASP group (P<0.05). It was concluded that rat UC model was established successfully. WMW could up-regulate the expression of IL-10, down-regulate the expression of TNF-alpha, IL-6, IL-8, and inhibit the NF-kappaBp65 activity to adjust immune function, indicating WMW had better curative effects on UC in rats.