Aim. To investigate the function of Tremella fuciformis polysaccharides (TFPS) in LPS-induced inflammation and oxidative stress of macrophages. Methods. RAW264.7 cells were pretreated with TFPS and then stimulated with 0.1 mu g/ml LPS. NF kappa B, Akt, p38MAPK, MCP-1, and SOD-1 were analyzed by Western blotting. Cell viability was measured using MIT assays. Reactive oxygen species (ROS) production, real-time PCR, ELISA, and immunofluorescence staining were performed on RAW264.7 cells that were treated with LPS and/or TFPS to investigate the anti-inflammatory effect of TFPS. Results. LPS induced inflammation and ROS production and promoted the secretion of cytokines such as TNF-alpha and IL-6. LPS also enhanced the nuclear translocation of NF kappa B, which promoted inflammation by oxidative stress. However, pretreatment with TFPS profoundly inhibited the activation of Akt, p38MAPK, and NF kappa B and attenuated the expression of MCP-1 in macrophages. Meanwhile, TFPS also decreased cytokine and ROS levels and attenuated cell inflammation after treatment with LPS. Moreover, miR-155, one of the key small RNAs which regulate NF kappa B and inflammation in macrophages, was significantly downregulated. Conclusion. TFPS inhibits LPS-induced oxidative stress and inflammation by inhibiting miR-155 expression and NF kappa B activation in macrophages, which suggests that TFPS may be a potential reagent for inhibiting the development of inflammation.