The effects of polysaccharides from Chlorella pyrenoidosa on immunomodulatory activity were investigated in this paper. Phagocytosis of peritoneal macrophages was detected through ingesting chicken red blood cells (CRBC) test to evaluate nonspecific immune response. The cellular immune response was measured using the delayed-type hypersensitivity response to sheep red blood cells (SRBC) in terms of antibody titration level. Oral administration of C. pyrenoidosa polysaccharides, 1 g and 2 g kg−1 body weight significantly enhanced phagocytic rate (23.00 and 26.25%, respectively) and phagocytic index (0.30 and 0.36, respectively) compared with saline-treated control (P<0.05). The value of ear thickness rate was greatly elevated from 10.09% in saline-treated control to 16.22 and 19.48%, respectively in group treated with 1 g and 2 g kg−1 body weight polysaccharides (P<0.05). There was a significant correlation between the dosage of C. pyrenoidosa polysaccharides and antibody titre (r=0.99, P=0.019) and the antibody titre was significantly increased by 11.80, 21.90 as well as 39.80 in 2 g kg−1 bw compared to 10.30 in the control. Dietary supplementation with C. pyrenoidosa polysaccharides did not affect the growth of the mice during the experiment. These results indicated that immunomodulatory activities in mice were enhanced by administration of polysaccharides derived from C. pyrenoidosa.