Chickens experimentally infected with Marek's disease virus J-1 strain were used to evaluate the anti-Marek's disease virus (MDV) activity of sodium tanshinone IIA sulfonate (STS) in vivo. Chickens in same group were kept in one pen and control group chickens were housed in negative pressure isolator. Chickens were treated with different dose of STS or ABOB for 21 consecutive days. Peripheral T lymphocyte proliferation, expression level of IFN-γ and IL-10 in serum, and MDV load in spleen were determined. The results showed that the treatments with STS and ABOB could significantly increase stimulating index (SI) of peripheral T lymphocytes while the SI is dropping due to the MDV infection, SI of chickens in STS prevention groups were significantly higher than that in STS treatment group and ABOB group (P<0.05 or P<0.01); IFN-γ and IL-10 level of chickens in STS groups were higher than that in other groups (P<0.05 or P<0.01). The results of qPCR demonstrated that STS could inhibit the virus replication in spleen of chickens infected with MDV. These findings indicated that STS can be potentially applied as an anti-MDV drug and set a solid basis for further investigating the antiviral mechanisms of STS.