Objective To investigate whether Nuclear factor erythroid 2-related factor 2 (Nrf2) -mediated microglial phagocytosis and inflammatory response plays a role in hematoma clearance and functional recovery after intracerebral hemorrhage (ICH).Methods The ICH model was induced by injection of type Ⅳ collagenase. 34 C57BL/6 mice were randomly divided into 4 groups, sham, ICH, ICH+ monascin, and ICH + Xuezhikang groups. 8 Nrf2 knockout mice (Nrf2^-/-) was ICH +Nrf2^-/- group. Further, 72 hours after surgery, neurologic scores, and hemoglobin levels were analyzed. The brain expression of Nrf2, Cluster of differentiation 80 (CD80), macrophage mannose receptor 1 (CD206), recombinant human triggering receptor expressed on myeloid cells 1 (Trem1) / (tumor necrosis factor-α) TNF-α (pro-inflammatory cytokines), and (recombinant human triggering receptor expressed on myeloid cells 2) Trem2/ (brain derived neurotrophic factor) BDNF (anti-inflammatory cytokines) were quantified by Western blotting analysis. The expression of Nrf2, CD80, CD206, Trem1, and Trem2 were determined by immunofluorescence labeling method. Correlation analysis was performed between Trem1 and Trem2 and neurological function scores, and between Trem2 and hemoglobin content.Results Compared with ICH group, ICH + monascin and ICH + Xuezhikang groups enable the hemoglobin content decrease (P < 0.05) and the modified Garcia scores improve (P <0.05), and can realize up-regulated expression of Trem2, CD206, and BDNF (P < 0.05) and inhibition of Trem 1, CD80, and TNF-α in the meantime (P < 0.05); ICH + Nrf2^-/- group shows opposite results (P < 0.05). There is a high negative correlation between the amount of protein expressed of Trem1 and neurologic function scores (r = -0.956, P < 0.05), and the opposite is found between Trem2 and neurologic function scores (r = 0.936, P <0.05). Protein expression in Trem2 is negatively correlated with hemoglobin content (r = -0.473, P < 0.05).Conclusion Nrf2 can regulate the function transformation of microglia to exert influence on the hematoma clearance after cerebral hemorrhage; Nrf2 agonists Monascin and Xuezhikang can realize the up-regulated expression of Trem2, CD206, and BDNF to enhance the phagocytosis of microglia and promote the hematoma products clearance and nerve repair; Down-regulated expression of Trem1, CD80 and TNF-α can be simultaneously realized to inhibit the inflammatory reaction of microglia and reduce hematoma and neurotoxicity after hemorrhage, exerting the neuroprotective effect.