Background. Diabetic macular edema (DME) is a vision-threatening complication that severely impairs vision, and VEGF has a certain improvement effect on it as a growth factor. Objective. To assess the alterations of different aqueous humor cytokine concentrations after intravitreal antivascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). Methods. We searched PubMed, EMBASE, and the Cochrane Library from inception up to May 2022 for studies evaluating the alterations of different aqueous humor cytokine concentrations after intravitreal anti-VEGF treatment for diabetic macular edema. The estimates from eligible studies were meta-analyzed by the Hartung-Knapp/Sidik-Jonkman random-effects method. Egger's regression test was used to determine the publications' bias. A 95% confidence interval was calculated across studies. The analysis was performed using STATA (TM) Version 15 software. Results. Nine eligible studies involving a total of 209 eyes for our systematic review were identified through our search strategy. The mean differences in 1-month and 2-month changes of VEGF were 110.681 pg/ml (P < 0.001) and 283.474 pg/ml (P=0.003), respectively. The mean difference in 2-month changes of interleukin 6 (IL-6) was -24.784 pg/ml (P=0.037). The mean difference in 3-month changes of central macular thickness was 130.372 mu m (P < 0.001). Conclusions. Intravitreal injection of anti-VEGF exerts a protective effect on macular edema secondary to diabetic retinopathy by affecting various cytokine concentrations, especially reducing aqueous VEGF concentrations and interleukin 6 in patients with DME.