Objective To investigate the correlation between systemic immune inflammatory index (SII) and other metabolic indicators and diabetic epiretinal membranes (dERM). MethodsA retrospective case-control study. From March 2022 to July 2023, 81 patients (81 eyes) with dERM in Department of Ophthalmology, Affiliated Jinhua Hospital of Zhejiang University of Medicine School diagnosed by fundus screening were included in the study. A total of 81 patients (81 eyes) with diabetes who were matched in age, gender, and duration of diabetes and had no dERM or diabetic macular edema in both eyes during fundus screening were selected as the control group. All patients underwent optical coherence tomography (OCT) examination and laboratory tests for peripheral blood neutrophil, lymphocyte, platelet counts, serum albumin, blood lipids, uric acid, and glycosylated hemoglobin (HbA1c). SII was calculated. Random urine samples were collected for urinary albumin/creatinine ratio (ACR) testing. The OCT device's own analysis software obtained the macular volume coefficient, including central foveal thickness (CMT), macular volume, and average macular thickness. The macular volume coefficient, SII, serum albumin, blood lipids, uric acid, HbA1c, and ACR between the two groups were compared using paired t tests or Mann-Whitney U tests. Conditional logistic regression analysis was performed to evaluate the risk factors for dERM; Spearman correlation test was used to analyze the correlation between CMT, SII, ACR, disorganization of retinal inner layers (DRIL), intraretinal cyst (IRC), and hyper-reflective foci (HRF) in patients with dERM. ResultsThere were significant differences in CMT, macular volume, average macular thickness, SII, serum albumin, and ACR between the dERM group and the control group (Z=−7.234, −6.306, −6.400, −3.063, −2.631, −3.868; P＜0.05). Conditional logistics regression analysis showed that high SII [odds ratio (OR)= 3.919, 95% confidence interval (CI) 1.591-9.654, P=0.003] and ACR (OR=4.432, 95%CI 1.885-10.420, P=0.001) were risk factors for dERM. Spearman correlation analysis showed that HRF, IRC, DRIL were positively correlated with CMT (Rs=0.234, 0.330, 0.248; P=0.036, 0.003, 0.026); HRF was positively correlated with SII and ACR (Rs=0.233, 0.278; P=0.036, 0.012). ConclusionElevated SII and ACR are independent risk factors for the occurrence of dERM.