As an alternative to perfluorooctane sulfonate (PFOS), increasing usage of perfluorobutane sulfonate (PFBS) has led to ubiquitous presence in the environment. PFBS is also shown to potently disrupt the thyroid endocrine system. Considering the regulation of thyroid hormones in visual development, PFBS is likely to adversely affect the development and function of visual systems, which is a sensitive target of environmental pollutants. Therefore, the present study exposed marine medaka embryos to environmentally realistic concentrations of PFBS (0, 1.0, 2.9 and 9.5 mu g/L) for an entire life-cycle. After exposure until sexual maturity, eyes of adult medaka were dissected to directly investigate the ocular accumulation and toxicity of PFBS. For the first time, substantial accumulation of an environmental pollutant (i.e., PFBS) was observed in the eye tissue. PFBS exposure was also found to impair the visual development and function in a sex-dependent manner. In female medaka, weight of eyes was significantly decreased, while content of water was increased, probably resulting in higher intraocular pressure. Multiple neural signaling processes were also disturbed by PFBS life-cycle exposure, including cholinergic, glutamatergic, GABAergic and monoaminergic systems. Increased levels of norepinephrine and epinephrine neurotransmitters may adaptively decrease the intraocular hypertension in female eyes. In addition, proteomic profiling identified the visual proteins of differential expressions (e.g., beta and gamma crystallins, arrestin and lumican), which were significantly associated with visual perception and motor activity of eyes. Overall, this study found that PFBS was able to accumulate in the eyes and induce ocular toxicities. The susceptibility and sex-specific responses of visual systems to environmental pollutants warrants more works for a comprehensive risk assessment.