Cerebral infarction leads to developing local neuroinflammation that causes additional damage to brain tissue. However, anti-inflammatory process has been reportedly to serve a potential target for therapeutic strategy in cerebral infarction. Adipose tissue is as the largest endocrine organ that exerts systemic functions on the brain via releasing secretory factors such as exosomes. Adipose-derived stem cells (ADSCs) reportedly play a key role in pathophysiology and treatment of central nervous system diseases. ADSCs-secreted exosomes serve as extracellular vesicles and deliver bioactive molecules between cells and organs and modulating/triggering a wide range of cellular responses in recipient cells that and play an important pathophysiological role in human diseases. This study aimed to investigate the effectiveness of ADSCs-derived exosomes transfected with “miR-21-5p” in treatment of cerebral infarction though modulating the neuroinflammatory response and involved signaling pathway. We first used LPS-induced BV-2 cells to mimic neuroinflammation after cerebral infarction in vitro. Then, exosomes were isolated from ADSCs and characterized. Next, these cells were co-cultured with ADSCs-derived exosomes. Bioinformatics data analysis combined with literature research showed that “miR-21-5pi” was abnormally expressed/produced in cerebral infarction. Therefore, we further overexpressed and knocked down miR-21-5p_i in ADSCs. Meanwhile, the inflammatory cytokines and nitric oxide synthase levels were assessed. Exosomes inhibited neuroinflammatory responses by delivering “miR-21-5p_i” to microglia. To assess the relationships between “miR-21-5p_i” and signal transducer and activator of transcription 3 (STAT3), bioinformatics and luciferase reporter assays were used. The results of the studies demonstrated that “miR-21-5p” contributed to the neuroinflammatory response through controlling STAT3 expression. Additionally, we discovered STAT3 and “miR-21-5p_i” expression in clinical samples. This study clarified that exosomal “miR-21-5p_i” from ADSCs could significantly suppress neuroinflammatory response through targeting STAT3 pathway in cerebral infarction. This finding could provide an important theoretical basis for developing effective preventive or therapeutic method for cerebral infarction in clinical practice.