Microcystins (MCs), hepatotoxins from cyanobacteria, induce oxidative stress and pathological changes in fish that can be ameliorated with chemoprotectants such as vitamin E (vit E). This study investigated the time period after MCs exposure in which Trolox, a vitamin E analog, is effective against oxidative and histological damage in different organs of tilapia (Oreochromis niloticus). Fish were fed Trolox supplement (700 mg/kg diet) for 7 days, or received only commercial fish food, and then were exposed to a single oral dose of 120 microg/fish microcystin-LR, and sacrificed in 24, 48, or 72 h. The Trolox protective efficacy was evaluated based on lipid peroxidation (LPO), protein oxidation, enzymatic and non-enzymatic antioxidants, and a morphologic study. Regarding the oxidative stress biomarkers altered by MCs, the higher protective action of Trolox was observed 24 h post toxin exposure, although it extends also until 48 h in gills (superoxide dismutase (SOD), catalase (CAT)), and liver, where glutathione reductase (GR) backed to control values 48 and 72 h after the toxin application. Glutathione-S- transferase (GST) activity in the liver was ameliorated by the chemoprotectant after 24 and 48 h, although control values were not recovered. Trolox modulation of these biomarkers and its ability to quench free radicals explain the recovery of LPO values in all organs at 24 h and also in gills at 48 h. Histopathologically, Trolox efficacy was more evident after 72 h.