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In order to explore the effect and mechanism of Gooseberry anthocyanins (GA) on reducing the ceramide content to reduce Insulin Resistance (IR) in mice.Molecular docking, Real-Time PCR and Western Blotting were used to explore the molecular mechanism and the effects of different doses GA in high-fat diet (HFD) mice.The results showed that the binding energy of anthocyanins on CerS6 was in the range of -8.2 to 5.2 kcal/mol, with low energy parameters and good binding positions. GA could effectively inhibit visceral fat, liver index, TC, TG and LDL-C, and improved HDL-C, GSH-Px and SOD.GA decreased the level of Insulin sensitivity index from-5.15 to-4.54 and improved insulin sensitivity and insulin resistance in HFD mice. Real-Time PCR and Western blotting results showed that GA could reducemRNA levels of inflammatory factors IL-6 and TNF-α, inhibit the expression of CerS6,PKCζ, PPARγ, CD36 and enhance the expression of SphK2, Akt, p-Akt/Akt, ISR. This study revealed the molecular mechanism of improving insulin resistance of GA in S1P/Cer signaling pathway, and provided theoretical support for preventive treatment of obesity related diseases by polyphenols.