Objective:To investigate the mechanism of DOK1 recombinant adenovirus(Ad-DOK1)on the regulation of insulin sensitivity in palmitic acid(PA)-induced insulin-resistant hepatocytes(BRL-3A).Methods:The control,solvent and model groups were treated with normal medium,ethanol and palmitic acid to establish a cellular insulin resistance model of BRL-3A cells and to iden-tify the cellular model using cellular glucose uptake assay.The control,null and adenovirus DOK1 overexpression groups were transfect-ed with normal serum,negative virus and Ad-DOK1(51257-1)in insulin-resistant BRL-3A cells,and the transfection efficiency of ade-novirus was detected by flow cytometry,and the Western blot method was used to detect DOK1,IRSI,IRSII,p-PI3K,PI3K,p-AKT,AKT,SREBP1c protein expression levels.Results:Palmitic acid induction for 6 hours resulted in a decrease in intracellular 2-deoxyglu-cose(P＜0.05),down-regulation of DOK1 protein expression level(P＜0.05),no significant change in IRSI and IRSII protein ex-pression level(P>0.05),no change in p-PI3K/PI3K ratio(P>0.05),down-regulation of p-AKT/AKT ratio(P＜0.05),and SREBP1c protein expression expression levels were upregulated(P＜0.05).After transfection of cells with DOK1 recombinant adeno-virus of optimal MOI 60,compared with the normal control group,intracellular 2-deoxyglucose was elevated(P＜0.05),DOK1 protein expression level was up-regulated(P＜0.05),there was no significant change in the expression level of IRSI and IRSII proteins(P>0.05),no significant change in the p-PI3K/PI3K ratio(P>0.05),the p-AKT/AKT ratio was upregulated(P＜0.05),and the ex-pression level of SREBP1c protein expression was downregulated(P＜0.05).Conclusion:Ad-DOK1 may enhance insulin sensitivity of BRL-3A cells by regulating AKT and SREBP1c.