: To assess changes in aqueous humor (AH) levels of cytokines following dexamethasone intravitreal implant (DEX) injection for diabetic macular edema (DME). : Sixteen DME and cataract cases series study. Anterior chamber AH sampling was performed at baseline at DEX injection time (T1), cataract surgery 8 weeks afterward (T2), and whenever DME relapsed (T3) in order to assess changes in IL-1β, IL-3, IL-6, IL-8, IL-10, MCP-1, IP-10, TNF-α, and VEGF levels. : IP-10 and MCP-1 levels significantly decreased at T2 ( = .034 and = .044, respectively) compared to baseline (T1). Relapsed DME cases (T3) showed significantly higher levels of IL-6 ( = .028), IL-8 ( = .005), IP-10 ( = .013) and MCP-1 ( = .005) compared to T2. : IP-10 and MCP-1 AH levels seem to be related to DEX intraocular action, decreasing after injection and increasing when DME relapses. In addition, IL-6 and IL-8 may play a role in DME late evolution and clinical relapse beyond DEX effect.