AIM: To explore whether there is an inflammatory response in the contralateral eye after cataract surgery in the first eye, and try to explore the development of the inflammatory response. METHODS: In this paired-sample study, aqueous humor samples from 37 bilateral age-related cataract patients were collected just before each cataract surgery. Samples collected during the first-eye cataract surgery were marked as Group A, samples collected during the second-eye cataract surgery were marked as Group B. In addition, the samples were classified into five groups according to different operation intervals between the first and the second cataract surgery. Finally, the concentration of 13 selected cytokines (including TNF-α, IL-6, IL-8, CCL2/MCP-1, IL-6 Rα, IL-1 ra, MIP-1α, MIP-1d, CCL4, IL-2, CXCL9, TIMP-1, CCL11) in aqueous humor samples was detected by Luminex-200 (RnD) simultaneously in accordance with the manufacturer’s instructions. RESULTS: Among the 13 selected cytokines, there was statistically difference between the first and the second eyes in concentration of IL-6, MIP-1α, CCL2/MCP-1, TNF-α, MIP-1d, IL-2 and TIMP-1 (P<0.05), and the expression levels of all these seven cytokines in the second eyes were higher than those in the first eyes, and the concentration of IL-6 and MIP-1a in the second eyes was significantly higher than that in the first eyes (P<0.001). Compared with the first eyes, the concentration of CCL4, CCL11, IL-6Rα, CXCL9, and IL-1ra in the second eyes only showed slightly increase, while IL-8 showed a slight decrease, all with no statistically difference (all P>0.05). The concentration differences of IL-6, MCP-1/CCL2, IL-2, MIP-1d between the first eyes and the second eyes were most obvious at the third week after phacoemulsification combined with intraocular lens implantation (PHACO+IOL) in the first eye. CONCLUSION: This study revealed that there may be an inflammatory response in the contralateral eye after cataract surgery in the first eye, and the inflammatory response in the second eye appears to be most significant at the third week after phacoemulsification combined with intraocular lens implantation (PHACO+IOL) in the first eye.