PURPOSE: To report a case of Diffuse Subretinal Fibrosis (DSF) syndrome refractory to immunosuppressive therapy who was successfully treated with anti-tumor necrosis factor alpha (TNF)-alpha monoclonal antibodies infliximab. DESIGN: Interventional case report. METHODS: A 23-year-old male with bilateral choroiditis presented sudden dimness of vision associated to nasal scotoma in his right eye. Complete ophthalmic examination with appropriated clinical and laboratorial evaluations was carried out during all follow,up. Inform consent statement and Internal Ethics Board approval were also obtained for an open,label therapy schedule. RESULTS: Extensive temporal subretinal lesion in his right eye and DSF in the left eye were observed. The patient received intravenous infliximab infusion (5 mg/kg) schema. Four weeks after starting treatment his visual acuity improved with decrease in ocular inflammation. CONCLUSIONS: This report describes a case of DSF syndrome that responded remarkably well to infliximab treatment suggesting that TNF-alpha could play an important pathogenetic role in this syndrome.