Introduction Fecal lactoferrin is the direct expression of intestinal inflammation in Crohn’s disease. The aim of this study was to analyze the in vivo intimate correlation between intestinal inflammation and systemic inflammation in patients without clinically active disease. Patients and methods 27 patients who had undergone ileo-colonic resection for Crohn’s disease were enrolled. A complete check up with an assessment of the Crohn’s disease activity index was performed as well as blood tests and fecal lactoferrin levels assessment and serum cytokine (IL-1beta, IL-6, IL-12, TNFalpha and TGF-beta1) levels were dosed. Results After a median follow up of 41 (17-87) months, the patients were in remission: CDAI 71.5 (56.9-112.7). The median level of lactoferrin were 11.53 (3.8-51.0) ug/g. Fecal lactoferrin levels significantly correlated directly with IL-6 (R=0.431, p=0.025) and CRP (R=0.507, p= 0.007). No correlation between lactoferrin and IL-1beta, IL-12, TNFalpha or TGF-beta1 was observed. Conclusions Subclinical intestinal inflammation in CD, expressed by fecal lactoferrin, seems to keep the systemic inflammation burning under the ashes through the IL-6-CRP cascade. The role of IL-1beta, IL-12, TNF-alpha and TGF-beta1 is probably more complex and less directly related to mucosal neutrophil infiltration.