Objective To investigate the protective effect of uric acid on PC12 cells injured by oxygen-glucose deprivation/reperfusion (OGD/R), and explore the mechanism. Methods Rat PC12 cells cultured in vitro were divided into control group, uric acid group, OGD/R group and OGD/R+uric acid group based on different ways of treatment. The cell viability was assessed by the modified MTT method, Annexin V-FITC/PI double staining was employed to determine the apoptosis rate, dihydrorhodamine (DHR) was applied to measure the cellular reactive oxygen species (ROS) levels, and rhodamine 123(Rh123) was used to detect the mitochondrial transmembrane potential (ΔΨm). Results The viability of PC12 cells in OGD/R group was significantly lower than that in control group (P<0.05), while management with uric acid (50-400 μmol/L) during OGD/R significantly increased the cell viability. Flow cytometry revealed that 400 μmol/L uric acid significantly inhibited OGD/R-induced apoptosis, reduced intracellular ROS production and decreased mitochondrial transmembrane potential, which were significantly different from those in OGD/R group (P<0.05). Conclusion Uric acid may have a neuroprotective effect against OGD/R-induced injury by attenuating ROS production and preserving mitochondrial function.