Lentinus edodes mycelia lowers cholesterol levels and acts as an immunomodulator and tumor-inhibitor in animal models. Lentinus edodes mycelia contains eritadenine (C₉H₁₁O₄N₅) and glucans among other biological compounds. However, whether or not Lentinus edodes mycelia is anti-atherogenic remains unknown. We examined the effect of Lentinus edodes mycelia (L·E·M) on atherosclerosis in a rabbit model. Thirty-two Japanese white male rabbits were fed with 1.0% cholesterol for 8 weeks, then divided into groups and given 1) 1.0% cholesterol for over 8 weeks (control), 2) 1.0% cholesterol and 1.0% L·E·M for over 8 weeks, 3) 1.0% cholesterol and 2.0% L·E·M for over 8 weeks, and 4) 1.0% cholesterol and 4.0% L·E·M for over 8 weeks (n=8 each group). Total cholesterol(TC) was measured periodically throughout the experiment. After the experimental periods, the aortas were removed and atherosclerotic lesions were examined histologically, immunohistochemically and morphometrically to determine surface involvement (SI) and an atherosclerotic index(AI). Body weight and TC did not significantly differ among the four groups. Decreases in SI were significant in the 1% L·E·M (26.2±10.8%) and 2% L·E·M (29.3±15.7%) groups compared with the control (48.7±15.3%;p < 0.05). The AI was significantly decreased in the 1% L·E·M(6.62±4.31) and 2% L·E·M (7.49±3.49) groups compared with the control (16.96±9.21;p < 0.05). Foam cells aggregated in thickened intima of dietary-induced atherosclerotic lesions in the rabbit aorta. In contrast, the numbers of foam cells in the intima decreased in the experimental group. No-cholesterol-lowering action or dose-dependant effects of L·E·M were determined in this study, but atherosclerotic development was significantly inhibited, indicating that L·E·M had anti-atherogenic properties. L·E·M may inhibit atherosclerotic development in rabbit aorta and be beneficial as a nutritional supplement.