In this study, we demonstrated that H. itama bee bread treatment significantly elevated SIRT1 and AMPK levels and the results were consistent with the reduced insulin resistance levels of lipogenic genes SREBP-1c and FAS, as well as levels of TG and TC in the liver, which might be accredited to its activation on Keap1/Nrf2 signaling pathway. Here, KEAP1 is linked to Insulin resistance.