Rhus verniciflua have been reported to inhibit immune systems through suppression of mitogen-activated protein kinases and nuclear factor-kB activation. Generally, low-molecular weight phenolic compounds, including EGCG and hydroxycinnamic acid derivatives, have anti-inflammatory effects. However, the mechanisms of action of high-molecular polyphenols on immunomodulating functions in murine leukocytes have not been characterised in detail. Numerous plants possess various polyphenols, and we regularly ingest polyphenol compounds as foods, which subsequently influence our health. Some polyphenols contained in functional foods and supplements are now used in alternative medicines. However, many foods contain not only phenolic compounds but also polyphenol-related enzymes such as polyphenol-oxidase and peroxidase. For instance, the edible mushroom, Agaricus brasiliensis possesses potent polyphenol-oxidase and peroxidase activities in the fruiting body ; and its extract gradually changes to brown colour, because of their enzymatic action. These facts led us to hypothesise that enzymatically polymerised polyphenols could contribute, at least in part, to the various beneficial effects of A. brasiliensis, such as its anti-tumour activity and various immunoenhancing properties. Phenolic compounds are easily converted to high-molecular weight polyphenols by various enzymes. Therefore, to facilitate the use of functional foods as alternative medicines, we decided to investigate whether high-molecular phenolic compounds exert immunomodulatory activities and their possible mechanisms. In the present study, we prepared polymerised polyphenols using horseradish peroxidase and hydrogen peroxide as an enzymatic source, and investigated the effect of enzymatically polymerised representative phenylpropanoic acids such as CA, FA, and CoA on immunomodulating activity. To confirm the immunomodulatory activity of polymerised polyphenols, in vitro cell culture with C57BL/6 mouse splenocytes in the presence of various polyphenols was performed. We first examined the cytotoxicity of our polymerised polyphenol preparations on murine splenocytes using the MTT assay. As shown in Figure 1, polymerised polyphenols did not induce any cytotoxic effects up to a concentration of 100 mg/mL. Comparatively, polymerised polyphenols, but not monomers, induced the proliferation of splenocytes in a dose-dependent manner, as reported previously. Next, we examined whether the polymerised polyphenols can induce cytokine production from murine splenocytes. Our results show that only the polymerised polyphenols, not the non-polymerised polyphenols, induced various cytokine productions from splenocytes.