Yi medicine Shekaqi is the most attractive traditional ethnic medicine due to its significant and diverse pharmacological activities. Two novel flavonoids, including 5,2'-dihydroxy-6-methoxy-7-decyloxyflavone and tenaxin II-7-O-β-D-glucuronopyranosyl acid butyl ester, along with six known flavonoids, were isolated from Yi medicine Shekaqi. Their structures were elucidated based on the analysis of their comprehensive spectral data. The in vitro lipid-lowering activities of the eight compounds showed that all the compounds significantly inhibited the lipopolysaccharide (LPS)-induced increase in the total cholesterol (TC) level, while compounds 1, 4, 6, 7, and 8 significantly inhibited the LPS-induced increase in the triglyceride (TG) level.