Goodea gracilis is an endemic fish that only habitats in some water bodies of Central Mexico that are contaminated with cyanobacteria-producing microcystins (MC); however, a lack of information on this topic prevails. With the aim to generate the first approximation about the physiological changes elicited by cyanobacterium that produce MC congeners in this fish species, specimens born in the laboratory was exposed for 96 h to cell densities of 572.5, 1145, 2290, 4580, and 9160 × 106 cells of Microcystis aeruginosa strain LB85/L, and a set of novel endpoint related to hepatic gluconeogenesis (ADH/LDH) and pro-oxidant forces , H2O2) in addition to biomarkers of oxidative damage and antioxidant response was evaluated in the liver. Results suggest that high inhibition of protein serine/threonine phosphatase (PP) may trigger many metabolic processes, such as those related to hepatic gluconeogenesis (ADH/LDH) and pro-oxidant , H2O2, TBARS, ROOH, RCO) as well as antioxidant (SOD, CAT, GPx) response to oxidative stress. Particularly, we observed that inhibition of LDH and PP, and H2O2 increase and TBARS production were the key damages induced by high densities of M. aeruginosa. However, changes between aerobic and anaerobic metabolism related with ROS metabolism and ADH/LDH balance are apparently an acclimation of this fish species to exposure to cyanobacteria or their MCs. Fish species living in environments potentially contaminated with cyanobacteria or their MCs possess mechanisms of acclimation that allow them to offset the damage induced, even in the case of fish that have never been exposed to MCs. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1113–1124, 2015.