Background: Inflammatory responses facilitate metastasis by increasing expression of adhesion molecules. Dietary restriction (30% reduction in daily calorie intake) reduces the expression of adhesion molecules and protects against surgically induced inflammation. DR might therefore beneficially interfere with surgery-induced inflammation and subsequent adhesion of circulating tumor cells. Methods: BALB/c mice were subjected to 2 weeks dietary restriction prior to inoculation with tumor cells. Intra-splenic injection of 5.0 x 10(4) C26-colon carcinoma cells was followed by splenectomy. Hepatic tumor load was scored after 10 days as a percentage (tumor surface/total liver surface) on H&E stained sections. Liver mRNA expression of adhesion molecules was determined and the effect of serum from dietary restriction mice on in vitro tumor growth and adhesion capacity was assessed. Results: Preoperative dietary restriction significantly reduced mRNA expression levels of E-selectin (P = 0.0087) and hepatic tumor load (P = 0.036). Dietary restriction serum did not affect in vitro cell growth but reduced in vitro adhesion of C26 cells to endothelial cells (P = 0.0043). Conclusions: Preoperative dietary restriction reduces hepatic tumor load after injection with tumor cells. Reduced adhesion to endothelial cells and reduced mRNA expression of E-selectin suggest that dietary restriction reduces tumor load by lowering the adhesion of circulating tumor cells to hepatic vascular endothelium. J. Surg. Oncol. J. Surg. Oncol. 2010; 102: 348-353. (C) 2010 Wiley-Liss, Inc.