〔Abstract〕 Objective To investigate the mechanism by which activation of α7nicotinic acetylcholine receptors (α7nAChR) optimizes brown adipose tissue (BAT) thermogenesis in obese mice. Methods Obesity was induced in C57BL/6J mice via a high-fat diet. Fifty 8-week-old mice were randomly assigned to five groups: low-fat diet (Control), high-fat diet (HFD), high-fat diet plus a β3-adrenergic receptor agonist (HFD+β3), high-fat diet plus a β3-adrenergic receptor agonist and an α7nAChR selective agonist (HFD+β3+GTS-21), and high-fat diet plus a β3- adrenergic receptor agonist and an α7nAChR selective antagonist (HFD+β3+α-BGT). Haematoxylin and eosin (HE) staining was used to evaluate BAT morphology. Transmission electron microscopy was performed to assess mitochondrial number and lipid droplet morphology in adipocytes. ELISA was used to measure levels of tumour necrosis factor-α (TNF-α), interleukin-lβ(IL-lβ), interleukin-10(IL-10), transforming growth factor-β (TGF-β), cyclic adenosine monophosphate (cAMP), and norepinephrine (NE). RT-qPCR was conducted to determine mRNA expression levels of vascular endothelial growth factor A (VEGF-A), nitric oxide synthase 2 (NOS2), arginase 1 (Arg1), uncoupling protein 1 (UCP1), PR domain-containing protein 16 (PRDM16), and peroxisome proliferator- activated receptor γ coactivator-lα (PGC-1α) in BAT. Immunohistochemistry was used to detect macrophage markers (CD3l, CD86, and CD206). Protein expression levels of UCPl, α7nAChR, nuclear factor-κB p65(NF-κB p65), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were analyzed by Western blot. Results Compared with the Control group, the HFD group showed enlarged lipid droplets and reduced mitochondrial numbers in adipocytes, accompanied by increased TNF-α and IL-lβ and decreased IL-10, TGF-β, Argl, and VEGF-A (all P<0.0l). Compared with the HFD+β3 group, the HFD+β3+GTS-21 group showed a smaller lipid droplet area and a higher mitochondrial number, along with reduced levels of pro-inflammatory factors, NOS2, and NF-κB p65, and increased levels of anti-inflammatory factors, Arg1, and phosphorylation of JAK2 and STAT3 (all P<0.01). Conclusion Activation of α7nAChR in combination with a β3-adrenergic receptor agonist effectively enhances thermogenesis, alleviates local adipose tissue hypoxia, and shifts the local inflammatory phenotype toward an M2-like state, thereby reducing inflammation in brown adipose tissue and improving its thermogenic capacity.