Objective To investigate the role of hesperitin in regulating inflammatory response in early brain injury after subarachnoid hemorrhage (SAH). Methods A total of 96 adult male SD rats were divided into sham-operated group, SAH group, solvent group and intervention group (n=24) by random number table method. The SAH rat models in the latter three groups were prepared by carotid artery puncture method; the rats in the intervention group were given oral administration of hesperidin solution, which was dissolved in 5％ dimethyl sulfolide (DMSO), with a concentration of 1 mg/100 μL and a dosage of 40 mg/kg within 30 min after operation; rats in the solvent group were given oral administration of an equal volume of 5％ DMSO solution. Modified Garcia behavioral scale was used to evaluate the neurobehavior of rats, and the wet/dry weight method was used to measure the water content in the brain tissues of the left and right hemispheres of the rats 24 h after SAH. Immunofluorescence staining was used to detect the microglia activation, Fluoro-dyed Jade C staining was used to assess the brain neuron degeneration, enzyme-linked immunosorbent assay (ELISA) was employed to detect the inflammatory factors interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) content in the brain tissues, and Western blotting was used to detect the nuclear factor-κB (NF-κB) and phosphorylated (p) -NF-κB protein expressions. Results As compared with the solvent group, intervention group had significantly increased improved modified Garcia behavioral scale scores (10.08±1.73 vs. 13.83±1.70), and significantly decreased water content of brain tissues in the left and right hemispheres ([81.44 ± 1.05]％ vs. ([79.14±0.82]％; [80.55±1.55]％ vs. [78.79±1.02]％), significantly smaller number of CD68+ and Iba1+ microglias (30.17±1.04 vs. 10.67±0.75; 29.33±1.16 vs. 12.00±0.41), significantly smaller number of degenerate neurons (53.21±0.94 vs. 31.33±0.28), significantly reduced levels of inflammatory cytokines IL-1β, IL-6 and TNF-α ([429.88±106.32] pg/mL vs. [221.50±48.80] pg/mL; [1015.50±221.80] pg/mL vs. [448.11±93.40] pg/mL; [1021.75±149.17] pg/mL vs. [595.71±190.81] pg/mL), and significantly lower p-NF-κB/NF-κB ratio (1.13±0.07 vs. 0.71±0.02, P<0.05). Conclusion Hesperitin may reduce the inflammatory response mediated by microglia after subarachnoid hemorrhage by inhibiting NF-κB pathway, thereby improving the neurological dysfunction of rats.