In order to make full use of brown algae Sargassum fusiforme, in the presence of pectinase and glucoamylase, the polysaccharide (SFP) from S. fusiforme was hydrolyzed to improve its biological activity. Single factor tests and response surface methodology were used to optimize enzymatic hydrolysis conditions based upon the degradation rate of SFP. Conditions for the hydrolysis of SFP were optimized as: hydrolysis temperature 54.2 degrees C, total enzyme concentration 68.5 U/mL, activity ratio of pectinase to glucoamylase 3.3:1, pH 6.0, degradation time 3 h. Under the optimized conditions, the degradation rate of SFP reached 18.6%. The antioxidant activities of the enzymatically degraded S. fusiforme polysaccharide (ESFP) prepared under the optimized conditions were greatly improved when compared to those of SFP. The IC50 values of ESFP on scavenging HO center dot, O-2(-center dot) and DPPH. were 4.78, 0.412 and 0.53 mg/mL, respectively; while those for SFP were 6.82, 0.723 and 0.768 mg/mL, respectively. The ferric reducing power of ESFP was also significantly higher than that of SFP. After incubation with RAW264.7 macrophages for 24 and 48 h, ESFP was found to possess significantly stronger activities in promoting cell proliferation, phagocytosis and NO release than those of SFP, indicating the superior immunoregulatory activity of ESFP.