In Crohn's disease (CD), clinical symptoms correspond poorly to inflammatory disease activity. Biomarkers, which reflect the level of intestinal inflammation are considered to enable effective monitoring of disease activity. The present study evaluated the role of serum pentraxin 3 (PTX3) as a marker of disease activity in patients with CD. Serum PTX3 levels were determined using an enzyme-linked immunosorbent assay in patients with CD (n=240), ulcerative colitis (UC; n=240) and healthy controls (HC; n=80). The expression levels of PTX3 were also evaluated in 35 fresh colonic tissue samples by western blot analysis. The association between levels of serum PTX3 with disease activity and its diagnostic role were analyzed. The levels of serum PTX3 were significantly increased in patients with active CD compared with patients in remission (UC and HC; P<0.01). A significant increase in the expression levels of PTX3 was identified at a protein level in inflamed colonic tissues compared with uninflamed colonic tissues. The levels of serum PTX3 were also positively correlated with disease activity in CD. These results indicated that serum and colonic expression of PTX3 were upregulated in patients with active CD, suggesting serum PTX3 is superior to CRP in predicting CD activity.