Obejective To explore protective effect of miR-29c on cerebral ischemia-reperfusion injury in rats. Methods Forty eight SD rats were randomly divided into sham group, model group, miR-29c NC group and miR-29c inhibitor group. Except the sham operation group, the other three groups were established by using ligation of middle cerebral artery. Twenty four hours after the operation, neurological behavior score, cerebral infarction volume, cell apoptosis, the activity of superoxide dismutase (SOD), the content of malondialdehyde (MDA), cysteine aspartic acid protease 3 (caspase 3), caspase 8, caspase 9, and the expression of miR-29c, Bcl-2, Bax, Bak1, cleaved caspase 3, cleaved caspase 8 and cleaved caspase 9. Results Compared with sham group, neurological behavior score, cerebral infarction volume, cell apoptosis rate was increased, SOD th the expression of miR-29c, activity was decreased, the level of MDA, caspase 3, caspase 8 and caspase 9 activity was increased. The expression of Bcl-2 was down-regulated, the expression of Bax, Bak1, cleaved caspase 3, cleaved caspase 8 and cleaved caspase 9 expression was up-regulated in model group, miR-29c NC group. The differences were also statistically significant (P<0.01). Compared with model group, miR-29c NC group, the expression of miR-29c, neurological behavior score, cerebral infarction volume percentage, cell apoptosis rate was decreased, SOD activity was increased, the level of MDA, caspase 3, caspase 8 and caspase 9 activity was decreased. The expression of Bcl-2 was up-regulated, the expression of Bax, Bak1, cleaved caspase 3, cleaved caspase 8 and cleaved caspase 9 expression was down-regulated in miR-29c inhibitor group. The differences were also statistically significant (P<0.01). Conclusion miR-29c had a protective effect on cerebral ischemia-reperfusion injury in rats, which was related to improve the antioxidant capacity and regulation of apoptosis related protein expression.