OBJECTIVE: To study the effects of carbamylated erythropoietin (CEPO) on cardiovascular microcirculation in rats with diabetes mellitus. METHODS: Rats were randomly divided into blank control group, model group, CEPO low-dose, medium-dose and high-dose groups (500, 1 000, 2 000 u/kg) with 12 in each group. The rats in the last 4 groups were reduced diabetes mellitus model. All rats were given relevant medicine intragastrically twice a week, coronary microcirculation endothelial cells were separated after consecutive 4 weeks. Enzyme-linked immunosorbent assay was conducted to detect levels of peripheral serum prostacyclin (PGI2), vasoconstrictor endothelin-1 (ET-1), angiotensin Ⅱ (AngⅡ) and von Willebrand factor (vWF) of rats in each group; in vitro CCK 8 test was used to detect endothelial cell activity (OD value); real-time quantitative polymerase chain reaction was adopted to detect proliferation-related genes (Ki67, p16), poptosis-related genes (Bad, Bax), and expressions of protein vascular endothelial growth factor (VEGF) and AngⅠ. RESULTS: Compared with blank control group, levels of PGI2, ET-1, AngⅡ and vWF in serum in model group increased; OD value deceased; Ki67, p16, Bax and VEGF expression decreased; the difference was statistically significant (P<0.05). Compared with model group, levels of PGI2, ET-1, AngⅡ and vWF in serum in CEPO low-dose, medium-dose and high-dose groups increased; OD value increased; Ki67, p16 and VEGF expression increased; expressions of Bad and Bax decreased; the difference was statistically significant (P<0.05). The others had no significant difference (P>0.05). CONCLUSIONS: CEPO maybe improve the coronary microcirculation function by upregulating VEGF expression in coronary microcirculation endothelial cells and promoting endothelial cells’ regeneration.