Objective To investigate the effects of crude Fomes officinalis polysaccharide ( FOPS ) and its purified constituent ( FOPS-a) on mitogen-activated protein kinases ( MAPK) signaling pathway and se-cretion of tumor necrosis factor-α (TNF-α) in RAW264. 7 macrophages. Methods RAW264. 7 macrophages were treated with FOPS and FOPS-a respectively at different concentrations (50, 100, 200 μg/ml) for 24 h. RT-qPCR and Western blot methods were respectively used to detect the expression at mRNA level and the phos-phorylated proteins of p38, c-Jun NH2-terminal kinase ( JNK ) and extracellular signal-regulated kinase ( ERK) . Changes in the phosphorylation of these proteins and TNF-α secretion were respectively detected by Western blot and ELISA after treating the macrophages with MAPK-specific inhibitors ( PD98059, SP600125, SB203580). Results Compared with the blank control group, different concentrations of FOPS and FOPS-a could significantly increase the expression at mRNA level and the phosphorylation of p38 and ERK (P<0. 05). Three inhibitors of MAPK could markedly decrease the phosphorylation of ERK1/2 and p38 and TNF-αsecretion that were induced by FOPS and FOPS-a (P<0. 05). Conclusions FOPS and FOPS-a might have immunomodu-latory effects on RAW264. 7 macrophages through activating ERK1/2 and p38 MAPK signal transduction pathways.