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Spontaneous intracerebral hemorrhage (ICH) is the deadliest stroke subtype and neuroinflammation is a critical component of the pathogenesis following ICH. Annexin A1‐FPR2 signaling has been shown to play a protective role in animal stroke models. This study aimed to assess whether Annexin A1 attenuated neuroinflammation and brain edema after ICH and investigate the underlying mechanisms. Male CD‐1 mice were subjected to collagenase‐induced ICH. Annexin A1 was administered at 0.5 hr after ICH. Brain water content measurement, short‐term and long‐term neurobehavioral tests, Western blot and immnunofluorescence were performed. Results showed that Annexin A1 effectively attenuated brain edema, improved short‐term neurological function and ameliorated microglia activation after ICH. Annexin A1 also improved memory function at 28 days after ICH. However, these beneficial effects were …