The aim of this study was to investigate the effect of rosiglitazone on the expression of Tumor Necrosis Factor-α (TNF-α) in the liver tissue of mice with Non-Alcoholic Steatohepatitis (NASH) and its role in NASH progression. Fifteen healthy male C57BL/6J mice were randomly divided into three groups: the control group (MCD+), the model group (MCD-), and the rosiglitazone group (MCD ± R). The serum alanine aminotransferase (ALT) and triglyceride (TG) levels were detected using the enzyme method. Hematoxylin-Eosin (HE) staining was performed to observe steatosis, inflammation, and fibrosis in the liver tissue. Reverse Transcription Polymerase Chain Reaction (RT-PCR) and western blotting were performed to detect the expression of TNF-α mRNA and protein. Liver pathology: the MCD+ group showed no significant liver steatosis, inflammation, and fibrosis; the MCD- group showed obvious steatosis and inflammation. However, the MCD ± R group exhibited reduced lesions. The expression of TNF-α mRNA and protein in the liver tissue among the groups was as follows: group MCD ≥ group MCD ± R>group MCD+. In the mouse models of NASH, the TNF-α expression in the liver tissue was related to the progression of NASH; Rosiglitazone can inhibit the expression of TNF-α and prevent the progression of NASH, thus providing new ideas for selecting therapeutic targets for NASH.