OBJECTIVE:To identify Cald1 as a novel regulator of Linggui Zhugan decoction(苓桂术甘汤)for im-proving insulin resistance in vivo and in vitro.METHODS:Sprague-Dawley rats were randomly as-signed to 3 groups that were received a normal rat chow diet,high-fat diet (HFD),and an HFD plus LG-ZGD,respectively.The homeostatic model assess-ment (HOMA)-insulin resistance (IR) index was used to determine IR.Gene microarray methodology was used to identify differentially expressed genes(DEGs) in the three groups of rats.The DEGs associ-ated with IR were confirmed by quantitative re-al-time polymerase chain reaction.Additionally,Mouse 3T3-L1 pre-adipocytes were differentiated into mature 3T3-L1 adipocytes,which were then treated with tumor necrosis factor (TNF)-α to in-duce cellular IR.Lipid accumulations were identi-fied by Oil Red O staining.Glucose uptake was as-sessed using the 3H-2-DG test.RESULTS:In this study,we found Cald1 was further screened to validate its biological function in 3T3-L1 adipocytes induced to develop IR.In vitro ex-periments showed that insulin-stimulated 3H-2-DG uptake by IR 3T3-L1 adipocytes was increased after LGZGD intervention,which was associated with a down-regulation of Cald 1 expression.CONCLUSION:LGZGD ameliorates HFD-induced IR in rats and TNF-α induced IR in adipocytes by down-regulating Cald1 expression.