To evaluate the role of vascular endothelial growth factor receptor-1 (VEGFR-1) in adhesion formation after laparoscopic surgery.Prospective, randomized study.Academic research center.Forty female Swiss mice.Adhesions were induced by standardized lesions during laparoscopy. The CO2 pneumoperitoneum was maintained for the minimum time needed to perform the lesions (10 minutes) or for a longer period (60 minutes) to evaluate basal adhesions and pneumoperitoneum-enhanced adhesions, respectively. Mice were treated either with IgG or with antibodies against VEGFR-1.Adhesions were quantitatively and qualitatively scored after 7 days during laparotomy.In IgG-treated mice, 60 minutes of CO2 pneumoperitoneum increased basal adhesions. In VEGFR-1 antibody-treated mice, basal adhesions were similar to the control group and 60 minutes of CO2 pneumoperitoneum did not increase adhesions. Therefore, in these mice, pneumoperitoneum-enhanced adhesions were lower than in IgG-treated mice.The data confirm that CO2 pneumoperitoneum is a cofactor in adhesion formation and demonstrate that VEGFR-1 plays a role in pneumoperitoneum-enhanced adhesions, which is consistent with a role of placental growth factor, VEGF-A, and VEGF-B in pneumoperitoneum-enhanced adhesions. These observations give new insight into the pathogenesis of adhesion formation.