Subarachnoid hemorrhage (SAH) is one of the life-threatening diseases with high morbidity and mortality rates. Small ubiquitin-like modifier (SUMO)-specific proteases 3 (SENP3), a member of the SUMO-specific protease family, was identified as an isopeptidase that deconjugates SUMOylation (The covalent modification by SUMO) of modified protein substrates. It is reported that SUMO-2/3 conjugation, a member of SUMOylation, presented neuroprotection. The study aimed to evaluate the expression of SENP3 and to explore its role potential role in SAH. A total of 95 Sprague-Dawley rats were randomly divided into sham group and SAH groups at 6, 12, 24, 48 h, day 3, day 5, and day 7. SAH groups suffered experimental SAH by injection with 0.3 ml nonheparinized autoblood into the prechiasmatic cistern. SENP3 expression is surveyed by western blot analysis, real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence. The levels of cleavage caspase-3 were determined by western blot and immunohistochemistry. SENP3 protein expression was significantly up-regulated after SAH which peaked at 24 h; however, the mRNA expression of SENP3 remained unchanged. Meanwhile, the level of cleaved caspase-3 was also increased after SAH. There is a highly positive correlation between cleavage caspase-3 and SENP3 in protein level. Immunofluorescent results showed that the expression of SENP3 was increased in neurons, rather than astrocytes nor microglia. Our findings indicated a possible role of SENP3 in the pathogenesis of early brain injury mediated by apoptosis following SAH.