One hundred and eighty Kunming mice were allotted to three groups in a randomized complete block design, including two treatments and one control. Mice in group 1 were fed a basal diet as control, while mice in groups 2 and 3 were fed the basal diet supplemented with 0.2 mg/kg selenium as sodium selenite (SS) or selenium-chitosan (SC), respectively. On day 28 of the experiment, blood selenium concentration, glutathione peroxidase (GPx) activity, plasma superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and Con A-induced splenocyte proliferation were determined, and plasma interleukin-2 (IL-2) and interferon-γ (IFN-γ) concentrations, splenic plaque-forming cell (PFC) responses, serum hemolysis level (HC50), and delayed-type hypersensitivity (DTH) responses were determined on day 15 of the experiment. The results showed that blood selenium concentration, GPx activity, splenic PFC response, and plasma IL-2 and IFN-γ concentrations in SC group were higher than those in the control and SS groups (P < 0.01 or P < 0.05), respectively. Plasma SOD activity, Serum hemolysis level, DTH responses, and Con A-induced splenocyte proliferation in SC group were higher than those in control (P < 0.01 or P < 0.05). Plasma SOD activity, serum hemolysis level, DTH responses, and Con A-induced splenocyte proliferation in SC group were also higher than those in SS group, while there was no significant difference between SC and SS groups (P > 0.05). Plasma MDA content in SC group was lower than those in the control and SS groups (P < 0.01 or P < 0.05). It is concluded that SC supplement can increase blood selenium concentration, antioxidation status, and cellular and humoral immunity, and SC has better biological activity than SS in mice.