Background The concentrations of cytokines in the aqueous humor from neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) may vary. The study was conducted to compare various cytokine levels in the aqueous humor of eyes with PCV, nAMD and control. Methods The present case control study included 49 treatment-naive eyes from 49 patients (PCV 24, nAMD 11, and cataract 14 eyes). Totally 34 angiogenic and inflammatory cytokines in the aqueous humor were measured by Luminex bead-based multiplex array. Results After adjusting for gender and age by multivariate logistic analysis, concentrations of IL-31, LIF, SDF1-alpha, VEGF-A, VEGF-D were significantly higher in eyes with nAMD or PCV compared with control eyes (all P < 0.05, times in nAMD: 59.5, 6.0, 7.0, 4.5, 5.6, respectively, times in PCV: 51.9, 5.21, 6.6, 4.0, 5.1, respectively), and concentrations of HGF, IP-10, MCP-1, IL-13 were significantly lower in eyes with nAMD or PCV than in control eyes (all P < 0.05, times in nAMD: 2.6, 2.0, 4.5, 4.7, respectively, times in PCV: 1.9, 3.0, 3.0, 2.8, respectively), but none of the 34 cytokines, including VEGF and IL-8, showed significantly different between eyes with nAMD and PCV. Conclusions Various cytokines involved in inflammation and angiogenesis including elevated IL-31, LIF, SDF1-alpha, VEGF-A, VEGF-D might be involved in the pathogenesis of nAMD or PCV. None of the 34 cytokines may help to differentiate nAMD and PCV.