In this study, we found that Rb1 treatment via oral administration reduced serum TG, LDL-c, and insulin in HFD-induced obese mice, and the lipid-lowering effect was further verified in a hyperlipidemia rat model, which indicated that Rb1 may improve hyperlipidemia, hyperinsulinemia, and insulin resistance in metabolic disorders. This evidence concerns the gene RB1 and metabolic disease.