Modified Si-Miao-San(mS MS) is composed of Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Coptidis Semen Coicis and Atractylodes Rhizome. The prescription is used for the management of diabetes and insulin resistance in the clinic. This study aims to investigate its regulation of glucose disposal in adipocytes. Differentiated 3T3-L1 adipocytes were stimulated with conditioned medium derived from activated macrophages to induce insulin resistance and observed the effects of Mac-CM on insulin-mediated glucose uptake along the insulin receptor substrate-1/PI3K/Akt signaling pathway. Moreover, its regulation of AMPK phosphorylation was also investigated. mS MS enhanced AMPK phosphorylation and promoted basal glucose uptake in adipocytes; mS MS inhibited NF-κB activation by reducing P65 phosphorylation and improved insulin-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to the restoration of insulin-mediated glucose uptake when cells were exposed to inflammatory stimulation. These beneficial effects were diminished in the presence of the AMPK inhibitor compound C. mS MS positively regulated AMPK activity, and this action contributed to improving insulin PI3 K signaling by the beneficial regulation of IRS-1 function through inhibition of inflammation in adipocytes. Modified Si-Miao-San (mS MS) is composed of Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Coptidis Semen Coicis and Atractylodes Rhizome. The prescription is used for the management of diabetes and insulin resistance in the clinic. This study aims to investigate its regulation of glucose disposal in adipocytes. Differentiated 3T3-L1 adipocytes were stimulated with conditioned medium derived from activated macrophages to induce insulin resistance and observed the effects of Mac-CM on insulin-mediated glucose uptake along the insulin receptor substrate-1 / PI3K / Akt signaling pathway. As the regulation of AMPK phosphorylation was also investigated. mS MS enhanced AMPK phosphorylation and promoted basal glucose uptake in adipocytes; mS MS inhibited NF-κB activation by reducing P65 phosphorylation and improved insulin-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to the restoration of insulin -mediated glucose uptake when cells were exposed to inflammatory stimulation se beneficial effects were diminished in the presence of the AMPK inhibitor compound C. mS MS positively regulated AMPK activity, and this action contributed to improving insulin PI3 K signaling by the beneficial regulation of IRS-1 function through inhibition of inflammation in adipocytes.