At present, the concentration of environmental pollutants, such as pesticides and antibiotics exposed in environment, especially in aquatic environment is increasing. These contaminants are exposed through aquatic environment to sh and ultimately accumulate in humans. Research on environmental pollutants has exploded in the past two years. However, there are still few studies on the combined effects of pesticides and antibiotics on sh, especially on sh gills. A separate analysis of the toxic effects caused by an environmental pollutant cannot fully show the real situation. In this paper, cypermethrin (CMN) and sulfamethoxazole (SMZ) were analyzed and found that there was a strong correlation between the pathways affected by the rst 30 genes regulated by CMN and SMZ respectively. Therefore, the toxic effects of CMN (0.651 μg/L) and/or SMZ (0.3 μg/L) on grass carp gill were studied in this paper. Histopathology, quantitative real-time PCR and other methods were used to detect the tissue morphology, oxidative stress level, in ammation and apoptosis-related indicators of the sh gills after exposure 42 days. It was found that compared with the single exposure (SMZ/CMN) group, the combined exposure (MIX) group had a more pronounced oxidative stress index imbalance. At the same time, nuclear factor-κB (NF-κB) signal pathway was activated and immuno-in ammatory reaction appeared in MIX group.This study reveals the harm of CMN and SMZ to sh, and provides a reference and basis for the rational use of pesticides and antibiotics.