Background The Arian broiler, an important native Iranian breed, shows heightened sensitivity to metabolic disturbances caused by lipopolysaccharide (LPS). This study evaluated whether glycyrrhizin could mitigate LPS‐associated physiological disruptions. Methods In a controlled trial, 100 Arian broilers (21‐day‐old, mean weight 750 g) were randomly allocated into five experimental groups: (1) ICV glycyrrhizin dose‐response assessment (1, 2 and 4 µg) evaluating feeding behaviour; (2) ICV LPS challenge (12.5, 25 and 50 ng) with 8‐h monitoring of feed intake and cloacal temperature; (3) IP glycyrrhizin administration (12.5, 25 and 50 mg/kg) to assess effects on feed consumption; (4) IP glycyrrhizin + ICV LPS interaction study; and (5) ICV glycyrrhizin + LPS co‐administration group. Results LPS administration induced characteristic biphasic temperature dysregulation, with significant hypothermia at 3 h (−1.3 ± 0.4°C vs. controls) followed by hyperthermia at 8 h (+1.1 ± 0.3°C), accompanied by feed intake reduction (p < 0.05). The findings indicated that feed intake increased significantly following the injection via both intraperitoneal and intracerebroventricular of glycyrrhizin in a dose‐dependent manner (p < 0.05), but IP delivery (25 and 50 mg/kg) showed comparable effects with 20–30 min delayed onset. Co‐administration completely prevented LPS‐induced disturbances at optimal doses. Conclusions Glycyrrhizin counteracts LPS‐induced thermoregulatory and feeding disturbances in Arian broilers through rapid‐acting mechanisms. While the physiological improvements align with anti‐inflammatory responses observed in other species, direct molecular evidence remains to be established.

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