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OBJECTIVE 3-N-butylphthalide (NBP) comprises one of the chemical constituents of celery oil. It has a series of pharmacological mechanisms including reconstructing microcirculation, protecting mitochondrial function, inhibiting oxidative stress, and inhibiting neuronal apoptosis and etc. Based on the complex multi-targets of pharmacological mechanisms of NBP, the clinical application of NBP is increasing and dried clinical researches and animal experiments are also focused on NBP. The aim of this review was to comprehensively and systematically summarize the application of NBP on neurological diseases and briefly summarize its application to non-neurological diseases. Moreover, recent progress in experimental models of NBP on animals was summarized. DATA SOURCES Literature was collected from Pubmed until November 2018,using the search terms including "3-N-butylphthalide", "microcirculation", "mitochondria", "ischemic stroke", "Alzheimer's disease", "vascular dementia", "Parkinson's disease", "brain edema", "CO poisoning", "traumatic central nervous system injury", "autoimmune disease", "amyotrophic lateral sclerosis", "seizures", "diabetes", "diabetic cataract", and "atherosclerosis". STUDY SELECTION Literature was derived from English articles or articles that could be obtained from English abstracts. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors' files. RESULTS NBP has become an important adjunct for ischemic stroke. In vascular dementia, the clinical application of NBP to treat severe cognitive dysfunction syndrome caused by the hypoperfusion of brain tissue during cerebrovascular disease is also increasing. Evidence also suggests that NBP has a therapeutic effect for neurodegenerative diseases. Many animal experiments have found that it can also improve symptoms in other neurological diseases such as epilepsy, cerebral edema, and decreased cognitive function caused by severe acute carbon monoxide poisoning. Moreover, NBP has therapeutic effects for diabetes, diabetes-induced cataracts, and non-neurological diseases such as atherosclerosis. Mechanistically, NBP mainly improves microcirculation and protects mitochondria. Its broad pharmacological effects also include inhibiting oxidative stress, nerve cell apoptosis, inflammatory responses, and anti-platelet and anti-thrombotic effects. CONCLUSIONS The varied pharmacological mechanisms of NBP involve many complex molecular mechanisms; however, there many unknown pharmacological effects await further study.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.