The present study showed that corticosterone (B) could induce a rapid activation of p38 and c-Jun NH2-terminal protein kinase (JNK) in PC12 cells. The dose–response and time–response curves were bell-shaped with maximal activation at 10−9 M and at 15 min. RU38486 had no effect, and bovine serum albumin-coupled B could induce the activation. Genistein failed to block the phosphorylation, suggesting the pathway was not involved in tyrosine kinase activity. Phorbol 12-myristate 13-acetate could mimic, while Gö6976 could abolish the actions. These results demonstrated that B might act via a putative membrane receptor to activate p38 and JNK rapidly through a protein kinase C-dependent pathway.