AIM: To quantitatively evaluate the effect of the combined use of 577-nm subthreshold micropulse macular laser (SML) and multi-point mode pan retinal laser photocoagulation (PRP) on severe non-proliferative diabetic retinopathy (NPDR) with central-involved diabetic macular edema (CIDME) using optical coherence tomography angiography (OCTA). METHODS: In this observational clinical study, 86 eyes of 86 NPDR patients with CIDME who underwent SML and PRP treatment were included. Images were obtained 1d before laser and post-laser (1d, 1wk, 1, 3, and 6mo) using AngioVue software 2.0. Best corrected visual acuity (BCVA, LogMAR), foveal avascular zone area (FAZ), choriocapillary flow area (ChF), parafoveal vessel density (PVD), capillary density inside disc (CDD), peripapillary capillary density (PCD), macular ganglion cell complex thickness (mGCCT), central macular thickness (CMT), and subfoveal choroidal thickness (ChT) were compared between pre- and post-laser treatment. RESULTS: BCVA remained stable during 6mo post-laser therapy (pre-laser vs 6mo post-laser: 0.53±0.21 vs 0.5±0.15, P>0.05). PVD, ChF, ChT, CMT, and mGCCT significantly increased 1d post-laser therapy [pre-laser vs 1d post-laser: superficial PVD (%), 40.51±3.42 vs 42.43±4.68; deep PVD (%), 42.66±3.67 vs 44.78±4.52; ChF, 1.72±0.21 vs 1.9±0.12 mm2; ChT, 302.45±69.74 vs 319.38±70.93 μm; CMT, 301.65±110.78 vs 320.86±105.62 μm; mGCCT, 105.71±10.72 vs 115.46±9.64 μm; P<0.05]. However, PVD, ChF and ChT decreased to less than baseline level at 6mo post-laser therapy (pre-laser vs 6mo post-laser: superficial PVD (%), 40.51±3.42 vs 36.32±4.19; deep PVD (%), 42.66±3.67 vs 38.76±3.74; ChF, 1.72±0.21 vs 1.62±0.09 mm2; ChT, 302.45±69.74 vs 289.61±67.55 μm; P<0.05), whereas CMT and mGCCT decreased to baseline level at 6mo post-laser therapy (CMT, 301.65±110.78 vs 297.77±90.23 μm; mGCCT, 105.71±10.72 vs 107.05±11.81 μm; P>0.05). Moreover, FAZ continuously increased while CDD and PCD continuously decreased in 6mo after laser therapy. CMT and ChT had a significant positive correlation with ChF and PVD in most post-laser stages. CONCLUSION: During a 6-month follow-up period after combined use of SML and PRP therapy, BCVA remained stable and there was a decreased trend in macular edema. Blood flow increased at 1d post-laser therapy and reduced at 6mo post-laser therapy.