Substantial evidence clearly indicates the immuno-inflammatory nature of atherosclerosis and the important roles of monocytes and other leukocytes in atherogenesis. The relationship between atherosclerosis and the peripheral monocyte count, however, has been equivocal and uncertain so far. One possible reason may be an opposing effect of different major risk factors of atherosclerosis on the monocyte count, e.g. smoking increases the monocyte count while hypercholesterolemia is accompanied by a lower monocyte count. Since smoking is well shown to increase leukocyte counts prominently in weeks, our study included only non-smokers who participated in a health check program at our hospital from 1996 to 1998 and had received a carotid duplex study with extra payment. Our results revealed the followings: In male non-smokers (n=571), the presence of carotid atherosclerosis was associated with significant increases in the counts of all leukocyte, neutrophil, and monocyte (P<0.005,<0.001 and <0.05, respectively), and, after adjustments for age and body mass index, there were significant positive links between these three leukocyte counts and the severity of carotid atherosclerosis, judged by either the sum score of all carotid plaques or the score of the most severe carotid plaque. On the contrary, in female non-smokers (n=614), there was no significant link between differential leukocyte counts and either the presence or severity of carotid atherosclerosis. These results are compatible with recently recognized sex differences in the mechanism and pathophysiology of atherosclerosis, and together with relevant results in the literature, suggest that monocytes and neutrophils are the main types of leukocytes involved in atherosclerosis.