To explore the molecular mechanism of the effect of Radix Astragali and its separated components on the lipid metabolism of rats with syndrome of dampness retention due to spleen deficiency.Methods:Rats with syndrome of dampness retention due to spleen deficiency were induced by complex factors of high fat and low protein diet，loading swimming for six weeks.And then，Radix Astragali and its separated components were administered to corresponding groups for two weeks，both pathological changes of the liverand gene expression changes related to lipid metabolism regulation were tested by using gene chip.Results:Morphological changes of the larger liver and bubble-like swelling of liver cells were detected in rats with syndrome of dampness retention due to spleen deficiency.Compared with the normal control group，genes of the PPARα pathway including fabp4，olr1 and cpt1b were down-regulated; me1，cyp7a1 and aqp7 were up-regulated in rats with syndrome of dampness retention due to spleen deficiency.Compared with the model control group，the number and degree of bubble-like swelling of liver cells in Radix Astragali and its separated components groups were decreased.Compared with the model control group，cyp7a1 was down-regulated，olr1and fabp4were up-regulated in rats of the decoction liquid of Radix Astragali group;aqp7 was down-regulated and fabp4was up-regulated in rats of Astragali flavone group; cyp7a1 was down-regulated，olr1and cpt1bwere up-regulated in rats of Astragalus polysaccharide group.Compared with the model control group，genes of the Linoleic acid metabolic pathway including pla2 g4a，pla2 g2d，cyp2c12 and loc687842wereup-regulated in rats of the decoction liquid of Radix Astragali group，pla2 g4a，pla2 g2d，cyp2c12 and loc687842 were up-regulated in rats of Astragali saponin group，cyp2c12 and loc687842were also up-regulated in rats of Astragalus polysaccharide group.Conclusion:Radix Astragali and its separated components(including Astragali flavones，Astragali saponin and Astragalus polysaccharide)obviously improved the abnormal morphology of the livers of rats with syndrome of dampness retention due to spleen deficiency，the mechanism of which may be the regulation of key genes of PPARα and Linoleic acid metabolic pathway.The key genes of PPARα pathway were me1，cyp7a1，aqp7，fabp4，olr1 and cpt1b，and the key genes of Linoleic acid metabolic pathway were pla2 g4a，pla2 g2d，cyp2c12 and loc687842.The Astragalus polysaccharide was proved to be the main substance in the regulation of lipid metabolism.