AIM: To determine the effects of laser photocoagulation on serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble angiopoietin receptor Tie-2 (Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor (VEGF) in patients with type 2 diabetes mellitus (T2DM) and proliferative diabetic retinopathy (PDR). We also explored the role of the Ang/Tie system in PDR.METHODS: 160 patients with T2DM, including 50 patients with non-diabetic retinopathy (NDR), 58 patients with non-proliferative diabetic retinopathy (NPDR), and 52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure.RESULTS: The median levels of Ang-2 and VEGF in serum were significantly higher in the NPDR group (4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group (2.67 ng/mL and 159.8 pg/mL, respectively, P<0.01), with the highest level in the PDR group (6.26 ng/mL and 531.2 pg/mL, respectively, P<0.01). The median level of Ang-1 was significantly higher in the NPDR group (10.77 ng/mL) compared to the NDR group (9.31 ng/mL) and the PDR groups (9.54 ng/mL) (P<0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups (1.49 vs 2.69 and 2.90, both P<0.01). The median level of Tie-2 was not significantly different among three groups (P>0.05). Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups (both P<0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased (both P<0.05), whereas serum Ang-1 level and Ang-1/Ang-2 ratio were weakly increased (P>0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group, however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups.CONCLUSION: Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2DM patients with PDR.