Objective To analyze the effects of Leizumab on the expression of proinflammatory cytokines in M1 macrophages in patients with severe proliferative diabetic retinopathy (PDR). Methods A retrospective study was conducted on 82 patients with severe PDR treated in the ophthalmology department of our hospital from January 2020 to January 2022, and they were divided into two groups according to different treatment methods, with 41 cases in each group. The control group was given vitrectomy (PPV) treatment, and the observation group was given 0.5mg intravitreal injection of leizumab one week before surgery on the basis of the control group. The number of neovascularization bleeding, operation time, clinical efficacy, macular fovea thickness (CMT), best corrected visual acuity (BCVA), serum vascular endothelial growth factor (VEGF), M1 macrophage proinflammatory cytokine expression, and total incidence of complications were compared between the two groups. Results The number of neovascularization bleeding in observation group was lower than that in control group (P＜0.05), and the operation time in observation group was shorter than that in control group (P＜0.05). The total effective rate of observation group (92.68%) was higher than that of control group (65.85%) (P＜0.05). After treatment, CMT and serum VEGF in the observation group were lower than those in the control group (P＜0.05), and BCVA in the observation group was higher than that in the control group (P＜0.05). After treatment, the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-23 (IL-23) in observation group were lower than those in control group (P＜0.05). The total complication rate of observation group (2.44%) was lower than that of control group (19.51%) (P＜0.05). Conclusion Leizumab can effectively shorten the operation time of PPV in patients with severe PDR, reduce the number of neovascular bleeding, improve visual acuity, inhibit the expression of M1-macrophage proinflammatory cytokines, reduce the thickness of macular fovea and the incidence of complications, with significant clinical efficacy