AIM: To observe the therapeutic effect of conbercept on diabetic macular edema (DME) complicated with diabetic nephropathy (DN). METHODS: In this retrospective study, 54 patients (54 eyes) that diagnosed as DME from January 2017 to October 2021 were collected. The patients were divided into two groups: DME patients with DN (25 eyes), and DME patients without DN (29 eyes). General conditions were collected before treatment, laboratory tests include fasting blood glucose, HbA1c, microalbumin/creatinine, serum creatinine. Optical coherence tomography (OCT) was used to check the ellipsoidal zone (EZ) and external limiting membrane (ELM) integrity. Central macular thickness (CMT), best corrected visual acuity (BCVA), and retinal hyperreflective foci (HF) as well as numbers of injections were recorded. RESULTS: There were significant differences between fasting blood glucose, HbA1c, serum creatinine, urinary microalbumin/creatinine, and estimated glomerular filtration rate (eGFR) between the two groups (all P<0.05). EZ and ELM continuity in the DME+DN group was worse than that in the DME group (P<0.05). BCVA (logMAR) in the DME group was significantly better than that in the DME+DN group at the same time points during treatment (all P<0.05). CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points (all P<0.05) and significantly decreased in both groups with time during treatment. At 6mo after treatment, the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86, respectively. CONCLUSION: Conbercept has a significant effect in short-term treatment of DME patients with or without DN, and can significantly ameliorate BCVA, CMT and the number of HF, treatment efficacy of DME patients without DN is better than that of DME patients with DN.