Objective To investigate the inhibition effect of salazosulfapyridine (SF) on the formation of post-operative abdominal adhesion and its possible mechanism. Methods Forty male Sprague-Dawley rats were randomly divided into five groups: sham operation group (Sham group), blank control group (BC group), sodium hyaluronate (HA) group, low dose of SF group (LSF group), and high dose of SF group (HSF group). Except the Sham group, all the rats in other 4 groups were created abdominal adhesion model by abrasion of caecum and its opposite abdominal wall. Rats of the BC group didn’t received any treatment after model establishment. Before closing the abdominal wall, the rats of the HA group were treated by 2 mL HA. After the operation, the rats of the LSF group and the HSF group were daily orally administrated with different dose of SF (50 mg/kg for the LSF group and 100 mg/kg for the HSF group), while the other 3 groups treated with same dose of normal saline. Seven days after operation, the rats of 5 groups were killed and abdominal adhesion conditions was evaluated by Nair’s score system. Then the abdominal adhesion tissues or blood were collected to underwent HE staining, immunohistochemistry staining, and enzyme linked immunosorbent assay (ELISA) test. The HE staining was used to assess the inflammation score and fibrillation score of rats in 5 groups and immunohistochemistry staining was used to evaluate expression of the α-smooth muscle actin(α-SMA) in adhesion tissues. The ELISA test was used to detect the concentration of serum interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) in rats of 5 groups. Results ① The gross evaluation of adhesion condition:3 rats of the Sham groups had incision adhesion; in the BC group, 4 rats had incision adhesion, 8 rats had cecum to the abdominal wall adhesion, 2 rats had viscera to viscera adhesion; in the HA group, 2 rats had incision adhesion and5 rats had cecum to the abdominal wall adhesion; in the LSF group, 2 rats had incision adhesion, 6 rats had cecum to the abdominal wall adhesion, and 1 rat had viscera to viscera adhesion; in the HSF group, 2 rats had incision adhesion and 4 rats had cecum to the abdominal wall adhesion. Compared with the Sham group, the Nair’s scores of the other4 groups were higher (P<0.05); compared with the BC group, the Nair’s scores of the HA group, the LSF group, and the HSF group were all lower (P<0.05), but there was no significant difference on the Nair’s scores among the HA group, the LSF group, and the HSF group (P>0.05). ② Inflammation score and fibrillation score: on the inflammation score, compared with the Sham group, the inflammation scores of the others 4 groups were higher (P<0.05); compared with the BC and HA group, the inflammation scores of the LSF group and the HSF group were both lower (P<0.05); compared with the LSF group, there was no significant difference on the inflammation score of the HSF group (P>0.05). On the fibrillation score, compared with the Sham group, the fibrillation scores of the others 4 groups were higher (P<0.05); compared with the BC group, the fibrillation scores of the HA group, the LSF group, and the HSF group were all lower (P<0.05), but there was no significant difference on the fibrillation scores among the HA group, the LSF group, and the HSF group (P>0.05). ③ The expression scores of α-SMA: compared with the Sham group, the expression scores of α-SMA in the others 4 groups were higher (P<0.05); compared with the BC group, the expression scores of α-SMA in the HA group, the LSF group, and the HSF group were all lower (P<0.05), but there was no significant difference on the expression scores of α-SMA among the HA group, the LSF group, and the HSF group (P>0.05). ④ Concentration of serum IL-1β and TGF-β1: on the concentration of serum IL-1β, compared with the Sham group, the concentrations of serum IL-1β in the others 4 groups were higher (P<0.05); compared with the BC group, the concentrations of serum IL-1β in the HA group, the LSF group, and the HSF group were all lower (P<0.05); compared with the HA and the LSF group, the concentration of serum IL-1β in the HSF group was lower (P<0.05). On the concentration of serum TGF-β1, compared with the Sham group, the concentrations of serum TGF-β1 in the others 4 groups were higher (P<0.05); compared with the BC group, the concentrations of serum TGF-β1 in the HA group, the LSF group, and the HSF group were all lower (P<0.05); compared with the HA group, the concentrations of serum TGF-β1 in the LSF group and the HSF group were both lower (P<0.05), but there was no significant difference between the LSF group and the HSF group (P>0.05). Conclusion SF can reduce the formation of postoperative abdominal adhesion in rat models via inhibiting inflammation and fibrillation.