There was no significant difference between Irisin group and Control group (0.048 ± 0.028 vs. 0.052 ± 0.012, P > 0.05), indicating that the single use of irisin had no extra effect on atherosclerotic lesion area, while the positive area/total area of Nicotine group was significantly higher than Nicotine + Irisin group (0.103 ± 0.011 vs. 0.048 ± 0.015, P < 0.001), suggesting that irisin could reverse nicotine-induced atherosclerosis. This evidence concerns the gene FNDC5 and atherosclerosis.