BACKGROUND AND PURPOSE: ST2, a member of the interleukin-1 (IL-1) receptor family, along with its ligand IL-33, plays critical roles in immune regulation and inflammatory responses. This study investigates the roles of endogenous IL-33/ST2 signaling in subarachnoid hemorrhage (SAH) and elucidates the underlying mechanisms. METHODS: Dynamic changes in endogenous IL-33 levels were examined following SAH induction in vivo. Rats underwent the endovascular perforation model of SAH and were randomly assigned to receive either recombinant IL-33 (rIL-33) or a vehicle, administered intranasally 1 h post-SAH. ST2 siRNA or an AKT selective inhibitor was administered intraperitoneally (i.p.) 48 h prior to SAH induction to explore the potential mechanisms of IL-33-mediated neuroprotection. RESULTS: Endogenous IL-33 and ST2 levels were elevated in in vitro models of SAH. Exogenous IL-33 significantly alleviated neuronal apoptosis, reduced brain edema, and enhanced short-term neurofunction in a dose-dependent manner following SAH in rats. CONCLUSION: Exogenous rIL-33 alleviates SAH-induced neurological deficits by promoting M2-like polarization of microglia post-SAH. These findings suggest a potential role of the microglial ST2/AKT axis in IL-33-related neuroprotection, which warrants further investigation.