Objective To investigate the expression of CD40-CD154 co-stimulatory pathway in peripheral circulation and intestinal mucosa in patients with inflammatory bowel disease (IBD), the difference between the expression of CD40-CD154 in patients with IBD and that in healthy controls, and the correlation between CD40-CD154 levels and disease activity. Methods A total of 62 patients with Crohn's disease (CD), 64 patients with ulcerative colitis (UC) and 56 healthy controls were enrolled. Enzyme-Linked Immuno Sorbent Assay (ELISA), SYBR-green real time PCR and immunohistochemical assay were respectively applied to evaluate expression of CD40-CD154 in plasma, mononuclear cells of peripheral blood and intestinal mucosa. Results Levels of CD40 ( P = 0. 000) and CD154 (P = 0. 001 ) in plasma, mononuclear cells of peripheral blood and intestinal mucosa were significantly higher in patients with CD and UC than in healthy controls. However, no correlation between disease activity and CD40-CD154 expression in peripheral circula- tion or intestinal mucosa was detected ( P 〉 0. 05 ). Conclusion CD40-CD154 pathway activation is found in plasma, peripheral blood mononuclear ceils and intestinal mucosa in patients with IBD, but is not correlated with disease activity. Key words: Colitis, ulcerative ; Complement pathway; Crohn's disease