Objective: To investigate the effect of CD40 siRNA on the myocardial pathologic changes, expression of Th17 cells specific transfer factor gene RORC mRNA of myocardium and concentration of Th17 cells related cytokines interleukin -17 (IL-17) and interleukin -23 (IL-23) in peripheral blood of rats with EAM. Methods: Forty 6-8 week old healthy male Lewis rats with body weight ranging from 185 to 210 gram were divided into EAM group (n=10), CD40 siRNA group (n=10), siRNA group (n=10), and control group (n=10) randomly. The rats in EAM group, CD40 siRNA group, and siRNA group were immunized with cardiac C protein and completed Freund adjuvant in double foot pads. The rats in control group were injected with PBS buffer in double foot pads. On the eighth day after immunization, rats in CD40 siRNA group and siRNA group were injected with CD40 siRNA expression vector and siRNA expression vector three times a week. These rats were sacrificed on day 21 after inoculation. The myocardial histopathologic changes were observed by light microscope and the myocardial histopathology scores were also calculated. The expression of RORC mRNA of myocardium was detected by real-time quantitative polymerase chain reaction (RQ-PCR). Enzyme linked immunoabsorption assay (ELISA) was used to determine the serum level of IL-17 and IL-23. Results: 1. Compared to EAM group, the myocardial histopathology scores in CD40 siRNA group significantly lower (13.33±5.56 vs. 17.00±2.16, P<0.05. 2. The expression of RORC mRNA in CD40 siRNA group decreased significantly compared to the EAM group (2.13±0.28 vs. 2.93±0.36,P<0.05). 3. The serum level of both IL-17 and IL-23 in CD40 siRNA group also decreased significantly compared to EAM group (both P<0.05). Conclusions: The results indicated that CD40 siRNA expression vector might reduce myocardial injury by inhibiting T helper lymphocyte IL-17 activation and down-regulating the expression of IL-17 and IL-23.