The mechanisms responsible for macular edema with branch retinal vein occlusion (BRVO) remain to be elucidated. It is known that the expression profile of certain proteins in the aqueous humor (AH) changes in some diseases. Accordingly, determining the expression of these AH proteins may aid in the understanding of their potential role in this pathogenesis. The aim of this study was to identify the possible mechanisms involved in the development of BRVO-induced macular edema. A proteomic analysis of the AH composition in the eyes of patients with BRVO was performed and compared with that in the eyes of patients with cataract (non-BRVO; controls). AH from 6 patients with macular edema due to BRVO and 6 patients with cataract (non-BRVO) was collected. A proteomic approach which included 2‑dimensional electrophoresis (2‑DE) coupled with mass spectrometry (MS) and bioinformatics analysis were used to identify AH proteins with altered expression in patients with macular edema due to BRVO compared with the controls. An enzyme‑linked immunosorbent assay was used to validate the proteomic results. The total protein concentration in the AH of patients with BRVO-induced macular edema was significantly greater than that of the controls. In the patients with BRVO, a total of 56 protein spots were significantly altered on the 2D gels. A total of 49 protein spots were identified by MS; many of these proteins have been implicated in angiogenesis, oxidative stress and collagen synthesis. In conclusion, the protein composition in AH differed significantly between the patients with BRVO and the controls. The identified proteins may be potential biomarkers for the development of macular edema due to BRVO and may play a role in the mechanisms responsible for it.