The present study investigated the protective effects of scutellarin on cobalt chloride (CoCl2)-induced apoptosis in PC12 cells. Incubation of PC12 cells with 500μM CoCl2 for 24h resulted in significant apoptosis as evaluated by the crystal violet, electron microscopy and flow cytometry assays. The increase of caspase-3 activity, decrease of Bcl-X(subscript L) expression, phosphorylation of p38 mitogen-activated protein kinase (MAPK) and accumulation of intracellular reactive oxygen species (ROS) were also seen in CoCl2-treated PC12 cells. Scutellarin at 0.1, 1 and 10μM significantly protected against the apoptotic cell death induced by CoCl2. Scutellarin decreased caspase-3 activity, increased Bcl-X(subscript L) expression, inhibited p38 phosphorylation and attenuated ROS production. These results demonstrate that scutellarin can protect PC12 cells from cobalt chloride induced apoptosis by scavenging ROS, inhibiting p38 phosphorylation, up-regulating Bcl-X(subscript L) expression and decreasing caspase-3 activity, and may reduce the cellular damage in pathological conditions associated with hypoxia-mediated neuronal injury.