Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-), and interleukin-2 (IL-2). We found the levels of serum IgG and INF- were significantly higher in late lactation cows after 300 and 400mg/day daidzein treatment compared to those in the control group and 200mg/day daidzein treatment (P<0.05 or P<0.01). Moreover, 300 and 400mg/day daidzein treatment markedly increased serum IL-2 (P<0.01), while the levels of serum TP and ALB were not changed by any concentration of daidzein treatment (P>0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress.