Increased fibrinogen (Fg) concentration in blood is a high risk factor for many cardiovascular diseases. We hypothesize that Fg and its early degradation product fragment D may result in arterial constriction through binding an endothelial intercellular adhesion molecule 1 (ICAM-1). The vasoconstriction induced by Fg and fragment D was studied in third-order (3A) and second-order arterioles (2A) of Sprague-Dawley rat cremaster muscle in vivo, in aortic and femoral artery rings, and in the segments of first-order arterioles (1A) isolated from rat cremaster muscle. Intra-vascular infusion of Fg induced significant constriction of 3A and 2A (by 33.4 ± 3.4 % and 23.7 ± 4.3 % respectively) in vivo and was abolished in the presence of specific endothelin type A receptor blocker BQ-610. Fg and fragment D produced significant constriction of both aortic and femoral artery rings. Isolated 1A constricted in response to Fg (0.3 µM) and fragment D (3 µM) by 31 ± 1.4 % and by 12 ± 1.5 % respectively. Fluorescently labeled Fg and fragment D bound to the vascular wall, while the albumin bound to a significantly lesser degree. The binding of Fg and fragment D to the arteriolar wall and constriction of aortic and femoral artery rings as well as isolated 1A were abolished in the presence of anti-Fg and anti-ICAM-1 antibodies. These results indicate that Fg and fragment D binding to vascular wall through ICAM-1 may contribute to increased vascular tone and resistance that compromise circulation.