Introduction: The objective of the study was to find out the influence of Thioflavin-T (ThT) on obesity and fatty liver by investigating the adipokine hormones, and insulin serum level of male NMRI mice which were exposed to a high-fat diet (HFD). Methods: 50 adult male NMRI mice were separated into five groups: n=10. The control group was given a standard diet at twelve-week intervals. The sham group was nourished with HFD that lasted for 8 weeks, afterwards, the group received a standard diet and solvent water (0.5ml) by gavage (4 weeks). The experimental groups 1-3 were nourished with HFD (4% cholesterol, 60% fat) eight-week period. Then, the treatment period started in experimental groups by receiving a normal diet in addition to ThT with three doses (5,10 and 15 mg/kg, 0.5ml), via gavage (4 weeks). Results: HFD contributed to a substantial reduction in serum adiponectin levels and increased leptin serum in the sham group opposite to the control group (P< 0.001). However, the concentration of both adipokine hormones was significantly modified under the treatment of ThT in a dose-dependent manner. Insulin serum increased in the sham group significantly (P< 0.001), meanwhile, a significant decrease was shown in experimental groups 2, and 3 than in the sham group (P<0.01). ThT also reduced HOMA-IR in experimental groups. The introduction of ThT in varying doses led to the induction of polymorphonuclear cells in the liver tissue. Conclusion: Our findings propose that ThT can affect liver function and body weight by modulating the serum levels of adipokine hormones besides decreasing the level of insulin and HOMA-IR in mice fed with HFD.