Abstract: Eutrophication in aquatic environment caused the release of microcystin-LR (MC-LR) into a water body during a period of cyanobacterial blooms, which pose serious threat to the fish survival and public health. In this study, we cloned the cDNA sequence of zebrafish (Danio rerio) abcc2 gene, and explored its role in MC-LR detoxification. Our results showed that zebrafish abcc2, similar to its mammalian counterparts, played roles in transport of its fluorescent substrate MCB, and that MC-LR treatment induced its transcriptional expression. Overexpression of Abcc2 significantly improved the survival rates of ZF4 cells and zebrafish embryos exposed to MC-LR. Zebrafish Abcc2 mediates MC-LR resistance and tissue defense and toxicants excretion, but it's role the detoxification of MC-LR remains unclear. These data reveal molecular mechanisms of fish in preventing accumulation of MC-LR and provide theoretical fundamentals for breeding cultured fish strains with MC-LR-resistant ability.