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AIM: To investigate the mechanisms of sulfasalazine (SASP) in the treatment of ulcerative colitis (UC).METHODS: Changes of pathological signs and histological grading of 106 patients with active UC were observed before and after the treatment with SASP, 1 g, thrice daily for 6 wk.RESULTS: The effect of SASP on the vasculitis in lamina propria was 48.2% and 17.4% in the mild active UC (P＜0.001) and 68% and 26.7% in the moderate active UC (P＜0.001) before and after treatment. Fibroid necrosis of vessel wall was found in one case of mild UC and two cases of moderate UC before treatment and was not found after treatment. No thrombosis was found in mild UC before and after treatment, while thrombosis was found in one case of moderate UC before treatment. The effect on mucosal glandular abnormality was 30.4% and 13.0% in mild UC (P＜0.05), and 42% and 40% in moderate UC (P＞0.05) before and after treatment. The rate of eosinophil infiltration was 98.2% and 80.4% in mild UC (P＜0.01),and 100% and 91.1% in moderate UC (P＜0.05) before and after treatment. The effect on crypt abscess was 21.4% and 4.4% in mild UC (P＜0.05), and 48% and 13.3%in moderate UC (P＜0.001) before and after treatment.The effect on mucosal pathohistological grading was 2.00±0.84 and 0.91±0.46 in mild UC (P＜0.001), and 2.49±0.84 and 1.31±0.75 in moderate UC (P＜0.001)before and after treatment.CONCLUSION: SASP can improve small vessel lesions and crypt abscesses and reduce neutrophilic and eosinophilic leukocyte infiltration in inflammatory mucosa of UC.