Background and Aims Sleeve gastrectomy (SG) is an effective method for treating obesity, but the mechanisms through which it exerts its effects are not fully understood. The glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) signaling pathways are closely related to the chronic oxidative stress state and adipose inflammation associated with obesity. However, it remains unclear whether the therapeutic effects of SG impact this pathway. Therefore, this study investigates the effects of SG on the GLP-1/DPP-4 pathway, oxidative stress, and inflammatory response in the adipose tissue of high-fat diet-induced obese mice.Methods Thirty mice were fed a high-fat diet to establish an obesity model, while another ten mice fed a standard diet were the normal control group. The 30 obese model mice were randomly divided into three groups to undergo SG operation (model + SG group), and sham operation (model + sham operation group), or to receive no treatment (simple model group), respectively. After surgery, all groups were fed a standard diet for 4 weeks. Visceral fat tissue samples were collected, and pathological changes in adipose tissue were observed using HE staining. Immunohistochemistry and qRT-PCR methods were used to analyze the expression of GLP-1 and its receptor GLP-1R, DPP-4, NADPH oxidase 4 (Nox-4), antioxidant enzymes [manganese superoxide dismutase (MnSOD), glutathione peroxidase (GSH-Px), catalase (CAT)], macrophage surface markers (CD11b), monocyte/macrophage surface markers (CD68, F4/80), and pro-inflammatory factors [monocyte chemoattractant protein-1 (MCP-1), IL-1β, IL-6, TNF-α] in the adipose tissue.Results HE staining showed that all obesity model groups had monocyte infiltration and inflammatory responses in adipose tissue compared to the normal control group. However, these responses were weaker in the model + SG group than those in the simple model group and the model + sham operation group. Immunohistochemistry results showed that the expressions of GLP-1 and GLP-1R were decreased compared to the normal control group. In contrast, DPP-4 expression was increased, and the proportion of CD11b positive cells and Nox-4 expression increased in the adipose tissue of all obesity model groups. However, these changes were significantly weaker in the model + SG group than those in the simple model group and the model + sham operation group, with no significant differences between the latter two groups.qRT-PCR results showed that in all obesity model groups compared to the normal control group, the mRNA expressions of GLP-1 and GLP-1R were decreased, while the mRNA expression of DPP-4 was increased (all P<0.05); the mRNA expression of CD68, F4/80 significantly increased (all P<0.05), the mRNA expression of Nox-4 increased, while the mRNA expression of MnSOD, GSH-Px, and CAT significantly decreased (all P<0.05); MCP-1, IL-1β, IL-6, and TNF-α expression significantly increased (all P<0.05). However, the magnitudes of changes in these variables were significantly smaller in the model + SG group compared to the simple model group and the model+ sham operation group (all P<0.05). At the same time, there were no significant differences in the magnitudes of changes between the latter two groups (all P>0.05).Conclusion SG operation can effectively regulate the GLP-1/DPP-4 pathway in adipose tissue and inhibit the immune responses, oxidative stress, and abnormal expression of pro-inflammatory factors, thereby improving the inflammatory response in adipose tissue.