AIM: To evaluate the efficacy and safety of conbercept combined with 577 nm subthreshold micropulse laser (STML) for treatment of diabetic macular edema (DME). METHODS: A retrospective study was conducted. From October 2022 to March 2024, 72 patients diagnosed with DME at the outpatient clinic were enrolled. The patients were divided into two groups: the simple group (treated with conbercept alone) and the combination group (treated with 577 nm STML combined with conbercept). The following itmes were compared between the two groups: best corrected visual acuity (BCVA), central macular thickness (CMT), foveal avascular zone (FAZ), vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), retinal mean sensitivity (RMS), injection numbers, and the number of cases with adverse effects. RESULTS: The mean age of patients was 57.13±8.76 (range 34-77)y with DR history of 0.89±0.55y. With the progression of treatment, both groups showed significant improvements in BCVA, CMT, DCP vessel density, and RMS compared to baselines (all, P<0.05). At 3 and 6mo after treatment, the combination group exhibited significantly better outcomes in BCVA, CMT, DCP vessel density, and RMS than the simple group (P<0.05). During the treatment period, neither group showed significant improvements in FAZ and SCP vessel density (P>0.05), and no significant differences in FAZ and SCP vessel density were observed between the two groups (P>0.05). The average number of injections required in the combination group was lower than that in the simple group (3.33±0.68 vs 4.06±0.96, P<0.05). No other serious ophthalmic adverse events were observed in either group. CONCLUSION: Conbercept combined with STML has better outcomes for treatment of DME and less intravitreal injections compared to conbercept monotherapy.