Abstract: This paper reports the immunoregulation of Astragalus polysaccharide (APS) on macrophages from the head kidney of large yellow croaker (Larimichthys crocea). APS was isolated and purified from Astragalus for the experiment. The effects of respiratory burst and phagocytic activity on the macrophages were detected by flow cytometry. The effects of APS on the gene transcription level of three cytokines TNFα, IL-1β and IL-6 were determined by qPCR. Experimental results showed that 50，100，200，400，800 μg/cm3 APS could significantly inhibit the reactive oxygen species (ROS) of macrophages; 100，200，400，800 μg/cm3 APS could significantly inhibit the reduction of nitric oxide (NO); 50，100，200 μg/cm3 APS could significantly increase the phagocytic activity of macrophages with LPS stimulation in the large yellow croaker. 200 μg/cm3 APS could significantly enhance the expression of TNFα, IL-1β and IL-6 mRNA at 6 h, 12 h and 24 h. The results indicated that APS had a significant immunoregulation on the cultured macrophages from the head kidney of large yellow croaker.