Abstract: Objective To provide the theoretical evidence for the early diagnosis of diabetic cardiac autonomic nerve lesion by studying its relation with HGF and IL-6. Methods Sixty patients with type 2 diabetes mellitus (T2DM) admitted to Second Affliated Hospital of Hebei Medical University from October 2011 to November 2012 who underwent 24 h dynamic ECG and squatting test were included in this study. The patients were divided into groups A, B, and C according to their SqTv and SqTs (Group A: Two indications were normal; Group B: One indication was abnormal; Group C: Two indications were abnormal), and 30 healthy subjects served as a control group(group D). Results The serum HGF and IL-6 levels were significantly higher in T2DM group than in control group (430.950±180.019 pg/ml vs 180.056±47.535 pg/ml, 147.108±51.577 pg/ml vs 61.541±10.029 pg/ml, P＜ 0.01) and increased with the severity of diabetic cardiac autonomic nerve lesion. The HRV index was signifcantly lower in T2DM group than in control group. Conclusion The serum HGF and IL-6 level can be used as an important marker for the early prevention and treatment of diabetic cardiac autonomic nerve lesion in T2DM patients. Squatting test is well related with HRV and can be applied to screening diabetic cardiac autonomic nerve lesion in T2DM patients.