Abstract: 【Abstract】 Objective To investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/ fibroblast growth factorinducible 14 (Fn14) in the serum and colon tissue of Crohn’s disease (CD) and to elucidate whether the expression of TWEAK/Fn14 can be used as an indicator for intestinal fibrosis. Methods Blood samples from 67 CD patients and 33 healthy controls were collected to measure the level of TWEAK by ELISA. Meanwhile, colon samples from 29 CD patients received colectomy and the normal colon tissues from 15 patients with colon cancer were included. The expression of TWEAK and Fn14 in colon samples was analyzed by immunohistochemistry (IHC). The number of the cells with Fn14， αsmooth muscle actin (αSMA) double positive was measured by immunofluorescent double staining. Results The level of serum TWEAK in CD patients was higher than that in healthy controls ( P<0.01), which was positive correlated with colectomy ( r=0.295, P=0.015), intestinal stenosis ( r=0.290, P=0.017) and intestinal obstruction ( r=0.453, P=0.000 1). ROC analysis displayed the area under the curve of serum TWEAK for predicting intestinal stenosis in CD patients was 0.67 (95%CI 0.540.80， P=0.020). IHC results showed that the expression of TWEAK and Fn14 were increased in colon samples from CD patients with intestinal obstruction ( P<0.05). The number of Fn14 and αSMA positive cells was significantly increased in CD patients with intestinal obstruction ( P<0.05). Conclusion TWEAK/Fn14 pathway may play an important role in CD related intestinal fibrosis.