The extensively accumulation of nitrate in different water resources is currently regarded as one of the most pre -dominant threats facing aquatic organisms on worldwide scale. In recent years, a growing body of evidences have been attempting to uncover the influences of nitrate on fish growth and health, thereby evaluating its environ-ment security. However, the systematic assessment and intrinsic mechanism of such influences are apparently devoid. Hence, this investigation employed systematic analysis, meta-analysis and bioinformatic analysis to eval-uate the nitrate biotoxicity. We first speculated two levels of nitrate concentration according to forty-four pub-lished bibliographies. Systematic analysis indicated that the broad variations of fish sensitivity to chronic and acute nitrate exposures were found in juvenile and larval stage, respectively, comparing to egg. Meta-analysis further revealed that survival rate, CF and SGR were significantly improved in low nitrate concentration during chronic exposure. Such improvements were reflected by Total mean differences (TMD) and 95% CIs (Confidence Intervals): Survival rate (-4.06 [-7.67, -0.45]), Fulton's condition factor (CF) (-0.03 [-0.03, -0.02]) and Spe-cific growth rate (SGR) (-0.10 [-0.16, -0.04]). To trace the impact, the alternations of molecular expression and histology in brain, gill, liver, intestine, and blood suggested that the chronic and acute nitrate exposures could result in abnormal tissue structures and molecular dynamics. Moreover, omics analysis via integrating in-testinal microbiome (microbial composition; %) and liver transcriptome (Gene Ontology: biological processes) revealed that the low concentration exposure induced a weakly immune response in fish liver and it matched to the intestinal immune response. Overall, current study has filled the gaps in the field of nitrate toxicity. It could also provide a novel insight for the evaluation of pollutant toxicity on aquatic species. (c) 2021 Elsevier B.V. All rights reserved.