This work was supported by Key Disciplines of Wuxi (ZDXK005) and Major Projects of Wuxi Health and Family Planning Commission (Z201705) Background: In the past, standard rapid decompressive craniectomy was used to alleviate the secondary damage caused by high intracranial pressure. Recent clinical studies showed that controlled decompression may have a better curative effect than rapid decompression. However, the effect on controlled decompression in animals is unclear. Material/Methods: Totally 80 healthy male New Zealand rabbits were randomly divided into a sham group (n=20), a rapid decompression group (n=30), and a controlled decompression group (n=30). An intracranial hypertension model was induced by injecting saline into an epidural balloon catheter and reducing ICP slowly and gradually by use of a pressure pump. The model was evaluated and analyzed by general observations, imaging examination, ICP values, behavioral score, brain water content, Nissl staining, and caspase-3 protein detection. Results: The mortality rate was 36.7% (11/30) in the rapid group, 20% (6/30) in the controlled group, and 5% (1/20) in the sham group. The incidence of epidural hematoma in the controlled group was lower than in the rapid group (p<0.01). The ICP was significantly lower in the controlled group than in the rapid group (p<0.001), and the behavioral score in the rapid group was higher than in the controlled group (p<0.05). There was a marked difference in brain water content between the controlled group and the rapid group (p<0.01). Nissl staining demonstrated that the ratio of Nissl body in the controlled group was significantly higher than in the rapid group (p<0.01). WB detection showed the expression of Caspase-3 in the controlled group was lower than in the rapid group (p<0.05). Conclusions: The results show the advantages of use of controlled decompression with intracranial hypertension. The animal model we developed provides a platform for further research on controlled decompression.