Abstract Objectives Microglia mediated neuronal inflammation has been reported to be responsible for neurodegenerative disease. Isoquercitrin (IQC), widely found in fruits, vegetables and foods, has high bioavailability and offers many benefits of humans. Although IQC has been shown to possess pleiotropic biological activities, but its anti-inflammatory mechanism in microglia at molecular level remains largely unclear. Therefore, this study aimed to investigate IQC’s inhibition on inflammation within BV2 microglia cells induced by lipopolysaccharide (LPS) and the underlying mechanism. Methods The cell viability was tested by using the MTT assay and the No production was measured by Griess reagent. Inflammatory cytokines expression was determined by RT-qPCR and the expression of iNOS、COX2 and correlation factor of NF-κB and MAPK pathway were determined by RT-qPCR and western blotting. Results IQC does not affect the viability of LPS-stimulated microglia. IQC treatment inhibited LPS-triggered NO and PGE2 production, iNOS and COX2 expression and affected the mRNA levels of relative inflammatory cytokines. Moreover, IQC inhibited nuclear factor kappa B(NF-κB) and MAPK pathway activation mediated by LPS, thereby inhibiting the levels of inflammatory cytokines. Conclusions IQC exhibited remarkable anti-inflammatory effects and promised therapeutic potential for neural inflammation associated diseases.