AimTo investigate the effect and mechanism of Sitagliptin phosphate on inflammation and macrophage polarization in a mouse model of type 2 diabetes.MethodsIn vitro, Raw264.7 cells were cultured with a high concentration of glucose (HG) and sitagliptin phosphate (SIG). The levels of inflammatory factors and the regulation of macrophage polarization were investigated, and the differentially expressed genes between HG and HG+SIG intervention were analyzed and enriched through transcriptomics. In vivo, C57BL/6J male mice were treated with HFD+STZ to establish a type 2 diabetes mouse model were investigated the effects of regulation of macrophage polarization in the pancreas and visceral adipose tissue.ResultsIn vitro cell experiments and transcriptomics showed that Sitagliptin phosphate decreased the secretion of inflammatory factors IL-6 and TNF-α induced by high-glucose, and increased secretion of anti-inflammatory factor IL-10 by enhancing macrophage polarization. In vivo, the body weight and abdominal visceral fat weight, the ratio of visceral fat weight to body weight and fasting blood glucose were significantly increased in the DM group compared with the Control (P0.05). Mechanistically, Western blot showed that compared with the normal group, HG upregulated the expression of mTORc1 protein, P-65 phosphorylation and P-65 protein expression in Raw264.7 cells (P