Purpose: To investigate the changes in intraocular cytokines after ranibizumab treatment in patients with polypoidal choroidal vasculopathy (PCV).Methods: This multicenter, prospective study enrolled patients with PCV treated with three monthly ranibizumab followed by a <i>pro re nata</i> regimen for 24 weeks. Best corrected visual acuity, slit lamp examination, fundus photography, and optical coherence tomography were performed every 4 weeks. Aqueous humor was collected to measure intraocular cytokines at baseline, week 8, and the time of recurrence or week 20. The association of changes in intraocular cytokines with visual acuity, central macular thickness, central choroidal thickness, area of abnormal vessels, and polyp closure was assessed.Results: This study included 25 eyes. The mean patient age was 70.3 ± 6.1 years. The vascular endothelial growth factor (VEGF) concentration decreased at week 8, but only interferon (IFN)-γ, tissue inhibitors of matrix metalloproteinases (TIMP)-2, and monocyte chemoattractant protein (MCP)-2 decreased at the time of recurrence. The recurrence interval was positively associated with the baseline epithelial-neutrophil activating peptide (ENA)-78, interleukin (IL)-17, leptin, and transforming growth factor-β1, and baseline central macular thickness was positively correlated with the baseline fibroblast growth factor-4 and IL-10. Thick central choroidal thickness was associated with a low basic fibroblast growth factor and high IFN-γ at baseline. The MCP-3 and Tie-2 levels decreased in two eyes with polyp closure.Conclusions: Ranibizumab significantly reduced intraocular VEGF concentrations and consequently improved PCV. However, the cytokines IFN-γ, TIMP-2, and MCP-2, rather than VEGF, were associated with PCV recurrence. Further studies of intraocular cytokines involved in neovascularization in PCV are needed.