Atherosclerosis, the main lethal disease in the Western world, is associated with a cellular immune response in the arterial lesions and a humoral immune response directed towards oxidized lipoproteins, certain microbes and other antigens. The local immune response is dominated by macrophages and T cells, while to date, the role of B cells in lesions has been unclear. We analysed B‐cell involvement in lesions using the apolipoprotein E knockout mouse, an experimental model that develops accelerated atherosclerosis when fed a lipid‐rich diet. Both early fatty‐streak‐type lesions and full‐blown atherosclerotic plaques of these mice contained CD22⁺ B cells. They accumulated predominantly in the base of lesions, where high expression levels of vascular cell adhesion molecule‐1 (VCAM‐1) were observed in other cells. Cells expressing interleukin‐6 and tumour necrosis factor‐α were also detected and IgM was abundant in this region. These data show that B cells participate in atherosclerosis in this experimental model; the data also suggest that these cells may accumulate through VCAM‐1 expression by surrounding cells and may produce antibodies and proinflammatory cytokines. These factors are likely to be important in the pathogenesis of atherosclerosis.