Pachymic acid (PA) plays a neuroprotective role during cerebral ischemia/reperfusion. However, the protective mechanisms of PA in cerebral ischemia/reperfusion have been not fully determined. This investigation aims to explore the neuroprotective role of PA in ischemia/reperfusion via miR‑155/NRF2/HO‑1 axis. The N2a cell line was induced by hypoxia/reoxygenation (H/R) to simulate the neuronal damage that occurs during cerebral ischemia/reperfusion. PA was used to treat H/R‑induced N2a cells. An MTT assay was used to determine cell viability. The protein levels of Bcl‑2, Bax, heme oxygenase‑1 (HO‑1) and nuclear factor E2‑related factor 2 (NRF2) were measured via Western blot analysis. The level of apoptosis of N2a cells was determined by flow cytometry. The expression levels of miR‑155 and NRF2 were quantified by real‑time PCR. PA treatment inhibits the increase in apoptosis induced by H/R and also enhances the viability of cells exposed to H/R. PA reverses the increased expression of miR‑155 caused by H/R. Furthermore, H/R does not change the expression of HO‑1 and NRF2, but PA upregulates the expressions of HO‑1 and NRF2. Additionally, NRF2 is the target of miR‑155. Inhibiting miR‑155 contributes to increased cell viability and decreased apoptosis via targeting the NRF2/HO‑1 pathway. Overall, PA prevents neuronal cell damage induced by hypoxia/reoxygenation via miR‑155/NRF2/HO‑1 axis.