In this study, the most optimal extraction conditions as regards to the immuno-modulatory activity of Rubus coreanus were determined to be 500MPa with water at 60°C for 15min (HPE15). The extraction yield under these conditions was estimated to be 17.3%, which was higher than the yield obtained from the conventional extraction process (13.9%) with water at 100°C (NE100). For most cases, the extract obtained under a high pressure of 500MPa for 15min HPE15 contained higher concentrations of the three main phenolic compounds relative to the conventional extraction procedure; catechin — 5.48mg/L vs. 3.11mg/L, caffeic acid — 12.34mg/L vs. 10.14mg/L and ferulic acid — 6.94mg/L vs. 2.59mg/L. It was found that the high amounts of bioactive components in HPE15 had a stronger beneficial effect on the growth of human B cell (>20%) and NK cell (>15%). In addition, the secretion of cytokines, IL-6 (>10%) and TNF-α (>12%), and NO- (>20%) production from macrophages treated with the HPE15 extract was also higher than when the cells were treated with NE100. Based on these combined findings, we concluded that the immuno-modulatory activities of the HPE15 could be enhanced by simultaneous responses of high concentrations of key active components and their synergistic effects. These results clearly proved that high pressure treatment over the appropriate extraction time could effectively destroy the cell membrane and allow the solvents to easily penetrate into the cytoplasm, which can result in the large release of immuno-modulatory active components with less heat damage.High pressure processing has been used for preservation purposes with no or minimal heat treatment where high temperature processing should be avoided. But, this process has not much studied yet on extracting useful compounds which are sensitive to heat from many food resources including medicinal plants even though this technology has many other advantages including a high yield and rapid extraction time within one hour without the need for thermal energy as well as with few impurities.Therefore, the results from this work about analyzing the ultra high pressure extraction process could definitely contribute to wide ranges of food industries for improving extraction yields correlated to their biological activities, which can expand this technology to process various natural resources having much nutritive and functional values as well as to overcome the mechanical limitations of manufacturing ultra high pressure extraction machines.