In male C57BL/6J (B6) NASH model mice fed with high-fat and high-fructose diets, nicotine (400 μg/kg, i.p., or 5 mg/kg, feeding) could significantly reduce the serum levels of IL-6 and TNF-α, and the inflammation was inhibited by the ERK/NF-κB/iκB pathway, TLR-4, and α7 nAChR stimulation in isolated Kupffer and LPS-induced RAW264.7 cells. The gene discussed is TNF; the disease is metabolic dysfunction-associated steatohepatitis.