Microglia are resident innate immune cells that play an essential role in the development and surveillance of the central nervous system as well as the shared pathogenesis of neurodegenerative diseases. Microglia rapidly respond to multiple inflammatory stimuli and activate towards different phenotypes, such as pro-inflammatory and anti-inflammatory phenotypes. Cytokines, epigenetic and long non-coding RNA modulations have been shown to regulate microglial activation; however, the role of circRNAs in microglia-mediated neuroinflammation remains elusive. Here, we performed circRNA sequencing in IL-4-treated anti-inflammatory microglia and discovered 120 differentially expressed circRNAs. We systemically verified the identities of circRNAs by assays of PCR, RNase R treatment and fluorescent in situ hybridization (FISH), among others. We found that circAdgre1 promoted IL-4-induced anti-inflammatory responses and further conferred neuroprotective effects upon lipopolysaccharide (LPS) stimuli. Taken together, our results show that circRNAs might be possible therapeutic targets for microglia-mediated neuroinflammation and neurodegenerative diseases.