故事发生在西汉初年，成就一世功业的汉高祖刘邦驾崩，虽然生前平定了韩信、彭越、英布等开国功臣的叛乱，却无法阻止皇后吕雉（刘雪华 饰）的专权。在这个强势女人的阴影下，刘氏宗族惨遭屠戮，锦衣卫首领刘宣（赵文卓 饰）被迫充当吕氏鹰犬，对同族亲眷痛下杀手。他和兄长刘湘（孙岩 饰）共同喜欢吕后的侄女琴子（高圆圆 饰），这段复杂的感情无疑成为兄弟俩矛盾的根源。偶然机缘，刘宣结识了名医淳于意那个调皮顽劣却纯真可爱的女儿缇萦（贾静雯 饰），故事又朝着未知的方向发展。
乱世初定，汹涌的权力斗争中，爱恋的男女随波逐流……
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