Abstract: In order to explore the effect of Astragalus polysaccharides（APS） on Zearalenone（ZEA）-induced apoptosis of chicken thymocytes, chicken primary thymocytes were used as materials, and the safe concentration of APS on chicken thymocytes was detected by MTT method. Thymocytes were treated with 50, 100, 200 and 400 μg/mL APS and ZEA for 48 h, respectively, and the cell control group and ZEA model control were set, and the cell viability was detected by MTT method. RT-qPCR method was used to detect the mRNA expression of endoplasmic reticulum stress and apoptosis-related genes. The results showed that the safe concentrations of APS on chicken thymocytes were 50-400 μg/mL. Compared with the cell control, the ZEA model control could significantly reduce the cell survival rate（P＜0.01）, and the relative expressions of GRP78, ATF6, ATF4, Caspase-3 and Bax gene mRNA were significantly up-regulated（P＜0.01）. The relative expression of Bcl-2 gene mRNA was significantly down-regulated（P＜0.01）. Compared with the ZEA model control, different concentrations of APS+ZEA could significantly or extremely significantly improve the cell survival rate（P＜0.05 or P＜0.01）, and the relative expression of GRP78, ATF6, ATF4, Caspase-3, Bax gene mRNA was extremely significantly down-regulated（P＜0.01）; the relative expression of Bcl-2 gene mRNA was extremely significantly up-regulated（P＜0.01）. The results suggested that APS could play a protective role by inhibiting ZEA-induced apoptosis and restoring the activity of thymocytes.