Stroke is one of the main causes of disease-related mortality worldwide. Buyang Huanwu Decoction (BHD) has been used to protect against stroke and stroke-induced disability for several years in China. Studies have shown that BHD can relieve neuronal damage in rats with cerebral ischemia/reperfusion (I/R) injury. However, the mechanism remains unclear. A middle cerebral artery occlusion and reperfusion (MCAO-R) model was used in the present study. The animals were treated with BHD (5, 10 and 20 g/kg) or rapamycin. Infarct size and modified neurological severity score were calculated on day 5 following MCAO-R surgery. Cellular changes around the ischemic penumbra were revealed by hematoxylin and eosin and Nissl staining. The protein expression levels of nestin, brain-derived neurotrophic factor (BDNF), doublecortin on the X chromosome (DCX) and autophagy-related proteins (beclin 1, LC3-II and p62) in the peri-ischemic area of the brain were detected. The results demonstrated that post-surgical treatment with BHD reduced the brain infarct size and improved neurological deficits in MCAO-R rats. BHD protected against MCAO-R-induced neuronal impairment and promoted neurogenesis, increased the protein expression of nestin, BDNF and DCX and markedly enhanced autophagy by increasing beclin 1 and LC3-II and decreasing p62. Meanwhile, BHD promoted the expression of sirtuin 1 (SIRT1), an important regulator of autophagy. In conclusion, the present study suggested that post-surgical treatment with BHD could protect rat brains from I/R injury, potentially through the SIRT1/autophagy pathway.