Microglia plays important role in central nervous system immune surveillance and has emerged as an essential cellular component for understanding brain diseases. MicroRNAs (miRs) are small, noncoding RNAs that regulate the post-transcriptional expression of protein-coding mRNAs, which may have key roles in microglial activation in response to brain ischemia and other stressors. Primary cultured rat microglial cells were prepared, and then microglial activation model was established by oxygen-glucose deprivation (OGD) method. Morphological observation, CD11b/c immunofluorence, MTT assay and Propidium iodide staining were done to test microglia viability at different OGD time points (0, 5, 10, 15, 30, 60 min). qPCR were performed to detect the dynamic changes in expressions of inflammation-related miRs (146a, 21, 181a, 221, and 222) and brain-enriched miRs (124, 134, 9, 132, and 138) in resting microglia and after challenge with OGD for the same time points. The activation and viability of the microglia was time dependent. Similarly, expressions of different miRs in microglia were significantly upregulated and reached the peak at different time points before reaching the baseline level with extension of OGD. Our data demonstrates for the first time that OGD as a model of an ischemic insult modulates the expressions of some inflammation-related and brain-enriched miRs. These changes may help to explore the molecular basis of microglia activation on the post-transcriptional level in response to different time points of OGD.