Stroke is a major public health problem, with high mortality rates, and a high frequency of disability. Between 1990 and 2010, stroke increased from the fifth to the third leading cause of disability. In addition, its incidence has increased among younger people, with severe health consequences and increased social costs. There is evidence that physical exercise promotes neuroprotective effects when used as a therapeutic treatment. However, the mechanisms of neuroprotection are not yet well known. The objective of the study was to evaluate the expression profile of microRNAs miR-16, miR-21 and miR-155 and the CASPASE-3 and Bcl-2 genes previously related to apoptosis in the tissue (ischemic focus). Forty-eight Wistar rats were divided into four experimental groups: control group, ischemia group, ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 19 (4): gmr18594 L.B. Porsani et al. 2 exercise group and exercise + ischemia group. Before the ischemic procedure, the animals in the exercise and exercise + ischemia groups were submitted to a treadmill training protocol for four weeks. The training lasted 30 min a day at a speed of 18 m / min. For real-time PCR analysis, a fragment of the ischemic area was collected from each animal using a punch to analyze the expression of miRNAs; miR16, miR-21, miR-155, CASPASE-3 and Bcl-2 genes. In the animals that had physical exercise, there appeared to be a neuroprotective effect by the action of microRNAs and CASPASE-3, although no significant difference was observed. Further studies are needed to elucidate the role of apoptosis mechanisms in cerebral ischemia associated with physical exercise, as well as the role of microRNAs in the modulation of targets associated with this mechanism.