Objective The 14-3-3 family, a group ofmultifunctional acidic proteins, exists predominantly in the brain.Up-regulation of 14-3-3γ is neuro-protective and crucial in protecting astrocytes from ischemia-induced apoptosis with the mechanism through binding to phosphorylated Bad to prevent Bad from getting into mitochondria.Preconditioning, happening under non-lethal ischemia stress, can induce endogenous self-protection to enhance tolerance to the subsequent ischemic insult and promoting survival.Our group is to explore 14-3-3γ may be an indicative endogenous protective protein in astrocytes preconditioning.Methods Up-regulation of 14-3-3γ was identified by Western blot.Morphology and LDH assay were performed to detect the necrosis of astrocytes.Results We found JNK/c-Jur/ AP-1 pathway to be responsible for the up-regulation of 14-3-3γ in astrocytes under ischemia.We investigated the expression of 14-3-3γ after ischemia preconditioning for 0.5 h, 1 h and 2 h and detected that it remains in a high level after reverting back to normal culture condition in 72 h.Furthermore, we found out that preconditioning for 0.5 h and then reverting to 6 h of normal culturing condition could produce significant protective role facing ischemia again.Once JNK signaling pathway was inhibited, up-regulation of 14-3-3γ induced by preconditioning was abolished.Conclusion Our studies infer that 14-3-3γcould be one of the protective proteins induced during preconditioning.