【Abstract】 Objective To explore the regulatory effect of Xuefu Zhuyu decoction on ERK/MAPK signal pathway in rats with glioma. Methods 60 rats were randomly divided into blank control group, glioma group, Xuefu Zhuyu decoction group, temozolomide group and combination group, with 12 rats in each group. Except for the blank control group, the rat model of glioma was established by intracranial injection of glioma C6 cells. Xuefu Zhuyu decoction group was given Xuefu Zhuyu decoction according to 20g/kg, and temozolomide group was given temozolomide (25mg/kg), and rats in combination group were given Xuefu Zhuyu decoction and temozolomide in the same time, once a day for 5 weeks. The ratio of tumor weight to brain weight, tumor inhibition rate, and the percentage of CD4+CD25+ regulatory T cells and CD8+T cells in peripheral blood were measured. The levels of IL-2, IL-10 and TGF-β1 in tumor tissue were determined by enzyme linked immunosorbent assay (ELISA) kit, and the pathological changes were detected by hematoxylin-eosin (HE) staining. The levels of ERK and p38MAPK mRNA in glioma tissue were detected by real time quantitative polymerase chain reaction (qRT-PCR), and the expression levels of ERK and p38MAPK in rat glioma tissue were detected by immunohistochemistry. Results Compared with glioma rats, the ratio of tumor weight to brain weight, the number of CD4+CD25+ regulatory T cells in peripheral blood, IL-10, TGF-β1, ERK and p38MAPK mRNA level, protein level and immunohistochemical IOD level in tumor tissue were significantly decreased in Xuefu Zhuyu decoction group, temozolomide group and combination group (P＜0.05). The tumor inhibition rate, the number of CD8+T cells in peripheral blood and the level of IL-2 in tumor tissue were significantly higher than those in Xuefu Zhuyu decoction group and temozolomide group (P＜0.05). Conclusion Xuefu Zhuyu decoction combined with temozolomide can inhibit the tumor progression and regulate the immune function of glioma rats. The mechanism may be related to the regulation of ERK/MAPK signal pathway.