BackgroundInsulin resistance (IR) is considered as a major factor initiating type 2 diabetes mellitus and can lead to a reduction in glucose uptake that mainly occurs in the liver. Astragalus polysaccharide (APC), extracted from the traditional Chinese medicine, has been recorded to suppress IR. However, the underlying mechanism remains inadequately explored.MethodsIR was induced in HepG2 cells which further underwent APC treatment. Cell viability was determined by cell counting kit‐8 assay. Pretreatment with AG490, an inhibitor of signal transducer and activator of transcription 5 (STAT5) signaling, was performed for investigating the influence of STAT5 on APC. Glucose uptake level was reflected by 2‐deoxyglucose‐6‐phosphate content determined through colorimetric assay. Expression levels of insulin‐like growth factor 1 (IGF‐1), IGF‐1 receptor (IGF‐1R), phosphorylated‐STAT5/STAT5, and p‐protein kinase B (AKT)/AKT in the cells were assessed by Western blot. Radioimmunoassay (RIA) was used to detect IGF‐1 secretion in the cells.ResultsAPC at doses of 10 and 20 mg increased the viability of HepG2 cells with/without IR induction, and abrogated IR‐induced inhibition of glucose intake. Meanwhile, APC (10 mg) offset IR‐induced inhibition on the expressions of IGF‐1R and IGF‐1, the activation of AKT and STAT5, and the secretion of IGF‐1 in HepG2 cells. More importantly, the reversal effect of APC on IR‐induced alterations in HepG2 cells was counteracted by AG490.ConclusionAPC ameliorates IR in HepG2 cells through activating the STAT5/IGF‐1 pathway.