Abstract: Objective To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in breast cancer patients with different glucose metabolic status and their correlation with microvascular production. Methods The clinical data of 187 patients with breast cancer from January, 2013 to June, 2015 were retrospectively analyzed. According to the blood glucose level, 67 patients were assigned into diabetic patients (DM group), 50 patients with impaired glucose regulation in IGR Group, and 70 patients with normal glucose tolerance in NGT group. The expression of HIF-1α and VEGF protein was detected by immunohistochemistry. The microvessel density (MVD) was measured and its correlation with the levels of HIF-1α and VEGF protein was analyzed. Results The levels of BMI, FPG, 2 h PG, HbA1C and HOMA-IR among NGT group, IGR group and DM group were significant different and the latter group was higher than the previous group (P<0.05). In IGR and DM group, the proportion of lymph node metastasis and tumor > 2 cm was significantly higher than that in NGT group (P<0.05), however, there was no significant difference between the positive rate of lymph node metastasis and the size of tumor larger than 2 cm between IGR group and DM group (P>0.05). The positive expression rates of HIF-1α and VEGF in DM group were significantly higher than those in NGT group (P<0.05), but there was no significant difference between DM group and IGR group (P>0.05). Among the three groups, the number of MVD in NGT was lowest, in DM group was highest, the differences were statistically significant (P<0.05). In HIF-1α positive patients, the positive rates of VEGF expression in NGT, IGR and DM groups were 72.0%, 84.2% and 96.7%, respectively (P<0.01), and MVD level was also increased (P<0.01). However, there was no significant difference in the expression of VEGF and MVD between NGT, IGR and DM in HIF-1α negative patients (P>0.05). Conclusion HIF-1α may play an important role in promoting the formation of microvessels in breast cancer patients with type 2 diabetes mellitus. Monitoring HIF-1α may play an important role in predicting the invasion and metastasis of breast cancer.