This study aimed to investigate the effects of the glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 dual-receptor agonist tirzepatide (TZP) on epididymal white adipose tissue (eWAT) inflammation in high-fat/high-fructose (HFHFr) diet–induced obese mice and to elucidate the underlying mechanisms. In addition, the anti-inflammatory effects of TZP were compared with those of the GLP-1 receptor agonist semaglutide (Sema).