Atherosclerosis is a chronic inflammatory disease that involves the formation of plaque within the intima. The secreted glycoprotein Wnt5a is a non-cannonical member of the Wnt family. Wnt5a expression has been shown in granulomatous lesions of M. turberculosis infected patients and in macrophages upon stimulation with lipopolysaccaride in vitro. Wnt5a has been linked to Toll-like receptor – 4 (TLR-4) signaling and TLR-4 has already been identified in atherosclerotic regions suggesting a cross-talk between Wnt5a and TLR-4. These observations lead to the hypothesis that Wnt5a is involved in atherosclerosis. To test this hypothesis, immunohistochemical analysis was performed on murine samples from the aortic sinus to the aortic arch and human carotid arteries from patients undergoing endarterectomy. Human and murine atherosclerotic lesions were immunostained for Wnt5a and its receptor Frizzled 5 (Fzd5) along with TLR-4. All samples were positive for Wnt5a and Fzd5 in the macrophage dense regions and had coincident TLR-4 expression. Wnt5a expression was also found to be in the smooth muscle cell region (media) from the human samples. These findings demonstrate Wnt5a and Fzd5 expression in human and murine atherosclerotic lesions.