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Introduction: Focal cerebral ischemia followed by reperfusion causes ischemia/reperfusion (I/R) brain injury. I/R injury is a complex pathophysiological process involving inflammation and apoptosis in neurons. Previous studies reported the anti-inflammatory traits of the family Violaceae. We aimed to evaluate the effects of Viola spathulata pre-treatment on infarct volume (IV), neurological deficit score (NDS) and alterations in mRNA level of cyclooxygenase 2 (COX2) and caspase 3 (CASP3) in a rat middle cerebral artery occlusion (MCAO) model. Methods: Thirty-three male Wistar rats were randomly distributed in 4 groups: normal control, MCAO control, MCAO + 5 mg/kg V. spathulata and MCAO + 10 mg/kg V. spathulata. Two doses of V. spathulata extracts were injected intraperitoneally for 7 days before the onset of ischemia. Finally, IV, NDS and mRNA expression of CASP3 and COX2 genes were assessed 24h after reperfusion. Results: IV and NDS in MCAO rats were remarkably higher compared with normal control rats and pre-treatment with V. spathulata extracts markedly reduced IV and NDS in the core, penumbra and subcortical regions of MCAO rats. Also, the level of COX2 and CASP3 mRNA was higher in the MCAO control group relative to normal control. Pre-treatment with V. spathulata extracts markedly reduced CASP3 mRNA relative to MCAO rats. Conclusion: It was found that V. spathulata might reduce ischemic damage in the brain of MCAO rats partly by decreasing apoptotic effects of CASP3. Further research is recommended to investigate signaling pathways involved in apoptosis.