Objective To study the effect of compound Rehmannia granule on the activation of microglia in the substantia nigra and striatum, the expression of inflammatory factors, and neurobehavior in different rat models. Methods We established a 6-hydroxydopamine (6-ODHA) and a lipopolysaccharide (LPS) animal model by administering a two- point stereotactic injection into the substantia nigra, combined with an intraperitoneal injection of apomorphine. Rats were divided into sham, model (6-ODHA and LPS model groups), and compound Rehmannia granule intervention groups (DH + 6-OHDA and DH + LPS groups). Rats in the drug intervention group were given 7 g / ( kg·d) compound Rehmannia granule suspension by gavage, whereas rats in the sham and model groups were given 2 mL saline by gavage once a day for 6 weeks. Spontaneous rotation behavior induced by apomorphine was observed and recorded after the model was established (abbreviation for 0 weeks) as well as at 2, 4, and 6 weeks after intragastric administration. Tumor necrosis factor-α (TNF- α) and other inflammatory factors in the substantia nigra and striatum were detected using enzyme-linked immunosorbent assay (ELISA). Western Blot was used to detect the expression of ionized calcium-binding adaptor molecule 1 (Iba1) and other proteins in the substantia nigra and striatum. Results (1) For neuroethology, compared with the model groups ( i. e., 6-OHDA and LPS groups), the spontaneous rotation behavior of rats in the compound Rehmannia granule intervention group was significantly lower at 4 and 6 weeks (P< 0.05 and P< 0.001, respectively). (2) The ELISA result showed that compared with the model group, TNF-α and other pro-inflammatory factors in the substantia nigra and striatum of rats in the compound Rehmannia granule intervention group were significantly lower (P< 0.01 and P< 0.001, respectively). (3) Western Blot result showed that compared with the model group, the expression of Iba1 and other pro-inflammatory proteins in the substantia nigra and striatum in the compound Rehmannia granule group were significantly lower (P< 0.05 and P< 0.001, respectively). Conclusions Compound Rehmannia granule intervention inhibits the activation of microglia in the substantia nigra and striatum, downregulates the expression of TNF-α and proinflammatory factors, and attenuates the spontaneous rotation behavior of model rats.