Abstract: Objective To determine if Ganoderma polysaccharides can antagonize prostaglandin E2 (PGE2)-induced suppression of murine splenocyte interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) mRNA expression. Methods Mixed lymphocyte culture reaction was used as the experimental model. The expressions levels of IFN-γ and TNF-α mRNA were measured by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results After the cultures were treated with PGE2 for 4 h, IFN-γ mRNA expression was reduced as compared with the control, which was especially obvious when PGE2 concentrations exceeded 10 μmol/L (P<0.01). Ganoderma polysaccharides above 100 mg/L showed partial antagonistic effect against the inhibition of IFN-γ by PGE2 at the fixed concentration of 20 μmol/L. Further studies indicated that PGE2 (20 μmol/L) impaired the expression of TNF-α mRNA after an 8-hour incubation and Ganoderma polysaccharides above 100 mg/L could partially antagonize this effect. Conclusion Ganoderma polysaccharides can partially antagonize PGE2-induced suppression of murine splenocyte IFN-γ and TNF-α mRNA expression.