Abstract: Objective　To observe the influence of alpha-lipoicacid（ALA） on serum homocysteine（Hcy） level in obese rats fed with high-fat diet（HFD）. Methods　A total of 10 rats were selected randomly from 50 Wistar rats，and were fed as a normal forage group，whereas the other 40 rats received a HFD for 10 weeks. Its obese rat model was evaluated，and obese rats were randomly classified into 2 groups：HFD group and HFD+ALA group who were injected with ALA for 2 weeks intraperitoneally at a dose of 30 mg/kg. The Hcy，fasting blood glucose（FBG），fasting insulin（FIns），triglyceride（TG），total cholesterol（TC），high density lipoprotein cholesterol（HDL-C），low density lipoprotein cholesterol（LDL-C） and non-esterified fatty acid（FFA）in serum were determined. The insulin resistance index（IRI） was calculated homeostatic model assessment of insulin resistance（HOMA-IR）.Results　The obese rat models of 32 obese rats were obtained after 10 weeks′ HFD. Compered to the normal forage group，HFD group gained a higher levels of Hcy，FIns，IRI，TC，TG，HDL-C and LDL-C（P＜0.05）. FBG and FFA had no obvious difference between the 2 groups（P＞0.05）. Compared to the HFD group，HFD+ALA group had a lower levels of Hcy，FIns，IRI，TC，TG，HDL-C，LDL-C and FFA，and FBG had no obvious difference. FFA levels in HFD+ALA group were significantly lower than those in the HFD group and the normal forage group（P＜0.05）. Conclusions　Obese rats induced by HFD have a high level of Hcy. ALA can improve insulin resistance，and reduce the serum Hcy level.