Aim To study the regulatory effect and molecular mechanism of berberine preconditioning on inflammation and apoptosis during cerebral ischemia reperfusion (I/R) in rats. Methods 40 SPF-grade adult male SD rats were randomly divided into sham group, I/R group, berberine pretreatment group (BP group), BP+SIRT1 inhibitor EX527 group (BP+EX group). Berberine 100 mg/(kg·d) was intragastrically administered to BP group for 14 days, berberine 100 mg/(kg·d) was intragastrically administered and SIRT1 inhibitor EX527 5 mg/(kg·d) as intraperitoneally administered to BP+EX group before modeling. After 14 days, the brain I/R model was established by thread embolization. Neurological impairment score, TUNEL staining and Nissl staining were used to evaluate the degree of neurological impairment. The expression of SIRT1 pathway genes, mitochondrial pathway apoptotic genes and inflammatory factors were detected. Results The neurological deficit score, TUNEL positive rate and the expression levels of nuclear factor kappa B (NF-κB), P53, Bax, Caspase-9, Caspase-3, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), IL-6, intercellular adhesion molecule -1 (ICAM-1) in brain tissue of I/R group were significantly higher than those in Sham group, the number of positive Nissl and the expression levels of SIRT1, Bcl-xL in brain tissue were significantly lower than those in Sham group(P<0.05). The neurological deficit score, TUNEL positive rate and the expression levels of NF-κB, P53, Bax, Caspase-9, Caspase-3, TNF-α, IL-1β, IL-6, ICAM-1 in brain tissue of BP group were significantly lower than those in I/R group, the number of positive Nissl and the expression levels of SIRT1, Bcl-xL in brain tissue of BP group were significantly higher than those in I/R group (P<0.05). The expression levels of Bax, Caspase-9, Caspase-3, TNF-α, IL-1β, IL-6, ICAM-1 in brain tissue of BP+EX group were significantly higher than those in BP group, the expression levels of Bcl-xL in brain tissue of BP+EX group was significantly lower than those in BP group(P<0.05). Conclusion Berberine preconditioning can alleviate inflammation and apoptosis in rats during cerebral ischemia-reperfusion by activating SIRT1 pathway.