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Abstract: Pharmacochemicals usage in fish farming disease treatment can cause morphological and functional changes in absorption capacity, metabolism and excretion organs. The aim of this research was to evaluate the histopathological biomarkers in the gills, liver, kidney and skin of pacu (P. mesopotamicus), which have been infected with A. hydrophila and treated with oxytetracycline (OTC) and florfenicol (FFC). Fish were exposed to 2.4×107 mL−1 of A. hydrophila bacteria experimental infection and after 24h exposed to FFC treatment for ten days and OTC for seven days. OTC was not effective in the A. hydrophila control in pacu in up to 170.0mgkg−1 concentration. Nevertheless, FFC was 100% effective with 10.0mgkg−1 concentration. After the treatment, skin, gills, liver and kidney samples were collected and processed for histopathological analysis. A. hydrophila caused lamellar fusion, sub epithelial edema, mucous hypertrophy and hyperplasia, lining, pillar and chloride cells. Hepatocytes hypertrophy was observed on liver, as a result of the antibiotics metabolism and bacteria cell wall. The histopathological biomarkers show the effects of the presence of the A. hydrophila. The use of the antibiotic florfenicol decreases the bacterial action effectiveness on tissues evaluated. Thus, the histopathological biomarkers show the A. hydrophila effect and the antibiotics treatment. The skin and liver are exposure biomarkers for both. [Copyright &y& Elsevier]