Abstract: The glucose consumption activity of 9-substitued analogues of berberine was evaluated in L6 myotubes. It was found that the introduction of an ethoxy group on the 9-position of berberine was beneficial for the activity. 9-Ethoxy berberine analogue 2a exhibited superior activity to berberine in multiple dose levels, and the activity of 2a was 5.4 times as high as that of berberine at the dose of 1.25 μmol·L^-1. At the meantime, the potency on AMPK activation of 2a was 2.8 times of that of berberine at the dose of 10 μmol·L^-1. Therefore, the compound 2a is a promising scaffold for further modification.