Early cyanobacterial blooms studies observed that exposure to blue-green algae led to fish gills impairment. The objective of this work was to evaluate the toxic mechanisms of exudates of Microcystis aeruginosa (MaE) on fish gills. In this study, the toxic mechanism of MaE (2×106 cells/mL) and one of its main components phytosphingosine (PHS) with two concentrations 2.9 ng/mL and 145 ng/mL were conducted by integrating histopathology, biochemical biomarkers, and transcriptomics techniques in Sinocyclocheilus grahami (S. grahami) for 96 h exposure. Damaged gill tissue with epithelial hyperplasia and hypertrophy, remarkable Na+/K+-ATPase (NKA) enzyme activity, disrupted the redox homeostats including lipid peroxidation and inflammatory responses were observed in the fish of MaE exposure group. Compare to MaE exposure, two concentrations of PHS exposure appeared to be a trend of lower degree of tissue damage, NKA activity and oxidative stress, but induced obviously lipid metabolism disorder with higher triglycerides, total cholesterol and total bile acid, which might be responsible for inflammation responses in fish gill. By transcriptome analysis, MaE exposure were primarily enriched in pathways related to gill function and immune response. PHS exposure, with higher number of differentially expressed genes (DEGs), were enriched in Toll-like receptor (TLR), Mitogen-Activated Protein Kinase (MAPK) and NOD-like receptor protein 3 (NLRP3) pathways. We concluded that MaE and PHS were induced the inflammatory responses, with oxidative stress-induced inflammation for MaE exposure but lipid metabolism disorder-induced inflammation for PHS exposure. The present study provided two toxin-induced gill inflammation response pathways under cyanobacterial blooms, which could be a scientific basis for the ecological and health risk assessment in the aquatic environment.