Abstract: Objective: To determine whether plasma homocysteine （tHcy） levels were related to insulin resistance induced by high-fat diet in wistar rats. Methods: 16 Wistar rats were randomized into 2 groups : control group（n=8） was fed with normal feeds, high-fat diet was given to high-fat group（n=8）. 11weeks later, glucose tolerance test were performed, and serum insulin, fasting glucose and plasma homocysteine were detected. Viscus adipose was weighted and then calculated the ratio of viscus adipose and the body weight. Results: fasting glucose, fasting insulin, insulin resistance index （IRI）, and the viscus adipose were significantly higher in high-fat group than that in control group（P＜0.01）. And the plasma homocysteine was significantly lower in control group than that in high-fat group. Correlation analysis showed that fasting glucose, fasting insulin, IRI, were all the factors influenced the plasma homocysteine. Stepwise regression test showed only fasting glucose（r=0.504,P=0.031） and IRI （r=0.302,P=0.046）independently affected the level of plasma homocysteine.Conclusion: We conclude that insulin resistance correlates significantly with plasma tHcy in high-fat feeding rats. This relationship may need to be considered when evaluating the role of plasma homocysteine as a risk factor in patients with type 2 diabetes.