Aim To investigate the possible association between serum endostatin, serum vascular endothelial growth factor (VEGF) and the pathogenesis of macroangiopathy in type 2 diabetes mellitus (T2DM). Methods The determination of endostatin,VEGF levels in 100 T2DM patients including 34 cases without macroangiopathy (group N),40 cases with only one kind of macroangiopathy (group A), 26 cases with much more macroangiopathy (group B) and 30 healthy control subjects (group C) was made by ELISA assay. Results The levels of endostatin and VEGF in T2DM patients complicated with macroangiopathy(group A,group B) were significantly higher than those without macroangiopathy (group N,group C),(endostatin:32.4±15.6 μg/L and 35.1±20.2 μg/L vs. 11.2±8.6 μg/L and 9.9±6.7 g/L;VEGF:133.5±36.8 ng/L and 302.1±52.4 ng/L vs. 90.2±42.4 ng/L and 81.3±33.5 ng/L, p<0.01). There was no significant difference between endostatin, VEGF levels in group C and those in group N.It was not endostatin levels but VEGF levels that were significantly elevated between group A and group B in turn 133.5±36.8 ng/L vs.302.1±52.4 ng/L,p<0.01). There was a significantly positive correlation between endostatin and VEGF levels in Group A(r=0.540,p<0.01). Conclusion The study suggests that the variation of serum VEGF levels is closely associated with the initiation and progression of T2DM macroangiopathy and meanwhile VEGF together with endostatin possibly plays an important role in the pathological course of As based on homeostasis regulation.