AIM: To evaluate chorioretinal responses to intravitreal aflibercept injection (IAI) in patients with acute central serous chorioretinopathy (CSC). METHODS: Seventy-one eyes from 71 patients with symptomatic CSC for less than six months were included. Thirty-five eyes received a single IAI and 36 eyes were observed without treatment. Best-corrected visual acuity (BCVA), central subfield foveal thickness (CSFT), and subfoveal choroidal thickness (SFCT) were assessed at baseline and at 1, 2, and 3mo. RESULTS: The mean SFCT in the IAI group decreased at 1mo, rebounded at 2mo and remained stable at 3mo compared to the baseline, while significant change was not noted in the observation group. The mean CSFT decreased significantly during the 3-month study period in both groups, and was significantly lower in the IAI group at 1mo (P<0.001). A rebound of CSFT between 1 and 2mo was noted in 14 eyes (40.0%) in the IAI group and in 1 eye (2.8%) in the observation group (P<0.001). The significant visual improvement was achieved from 1mo in the IAI group, and from 2mo in the observation group. The rate of complete absorption of subretinal fluid at 3mo did not differ between the two groups. (45.7% vs 41.7%, P=0.813). CONCLUSION: A single IAI for acute CSC induce a transient decrease in SFCT and CSFT, which implies that IAI may have a pharmacological effect on the underlying hyperpermeable choroid in acute CSC.