Natural compounds found in Lignosus rhinocerus like polysaccharides and polysaccharide-protein complexes have the capabilities to modulate the immune system. It possesses antitumor and anti-inflammatory properties and is commonly used in Southeast Asia and Southern China to alleviate illness. To investigate its immunomodulating properties, composition of polysaccharides and the expression of cytokines/chemokines from L. rhinocerus (TM02®) cultivar treated RAW 264.7 were explored. It was revealed, CWE contains linear polysaccharides with 1,4-linkages and rhinoprolycan fraction (HMW & MMW) possesses 1,4-Glcp and 1,6-Glcp backbone and branched chain (1,3,6-Glcp, 1,4,6-Glcp, 1,3,6-Glcp, 1,2,4,6-Glcp). Cytokines profile showed upregulation from CWE (IL-5: 12.078 ± 1.225), HMW (IL-6: 7.297 ± 0.338; TIMP-1: 3.358 ± 0.200), MMW (IL-5: 15.412 ± 5.823; TIMP-1: 1.747 ± 0.053), and LMW (MIP-2: 3.495 ± 0.416; TIMP-1: 7.573 ± 0.088) and possible involvement of NF-κB and MAPK signaling pathway. Further in vivo studies are needed to fully understand the immunomodulatory effects of TM02®.