A study was carried out to test the response of genes involved in antioxidant and inflammation in head kidney macrophage to acute ammonia toxicity for 96 h. 0.14 and 0.28 mg/L total ammonia nitrogen (TA-N) groups had lower mRNA expression of SOD than that of fish in control, but the highest mRNA expression of GPX was found in 0.28 mg/L TA-N group; 0.14 and 0.28 mg/L TA-N groups had lower mRNA expression of IL-1 and TNF than those of control group, and 0.28 mg/L TA-N group had lower mRNA expression of IL-8 than that of fish in 0.14 mg/L TA-N and control groups; detection with acridine orange staining showed that irregular acridine signal were detected in fish head kidney macrophage cells (HKMC) exposed to 0.14 mg/L TA-N, while HKMC treated with 0.28 mg/L TA-N exhibited extremely high fluoresence intensity. This study indicated that ammonia exerts its toxic effects by interfering with the mRNA expression of antioxidant genes; the apoptosis may be one of the main causes of death caused by ammonia poisoning.