Alginate is polysaccharide easily extracted from brown algae. The objectives of t his study were to evaluate the effects of feeding intervals of sodium alginate (SA) from Padina australis on cellular-humoral immunity, the expression of immune genes, and disease resistance against Streptococcus agalactiae . R ed tilapia wa s fed with a commercial feed supplemented with SA at a dosage of 2 g kg-1 for 60 days, under the supplementation intervals of 0 (control), 1, 2, 3, and 4 days. The blood sample was taken on days 0, 3, 30, and 60 to evaluate the immune parameters. The cellular and humoral immune parameters were evaluated. T he expression of immune genes was measured on day 30 . Another experiment with the same treatments was conducted to evaluate the resistant of red tilapia against artificial infection of S. agalactiae . The fist mortality was observed for 7 days post infection. Results indicated that SA supplementation every 4 days was the most effective to improve the immune parameters of the fish . SA supplementation improve d T otal L eucocyte Count , phagocytic activity, respiratory burst, S uper O xide Dismutase , lysozyme, and complement. The expression of IL-1β, TNF -α, IFN -ɣ, and Hep genes were elevated , but downregulating the IL-10 and TGF-β1 was occured . Furthermore , the disease resistant of red tilapia against S. agalactiae was improved by supplementing SA. The results give the new perspective to utilize SA as immunostimulant by oral administration in practical aquaculture.