Abstract: Objective To determine the changes in phosphorylation of conventional protein kinase Cγ (cPKCγ)-interacting extracellular signal regulated kinase 1/2 (ERK1/2) in the hippocampus of hypoxic preconditioned (HPC) mice. Methods Healthy male BALB/c mice were used to develop "auto-hypoxia"-induced HPC mice and randomly divided into 3 groups as follows: normoxic control (H0), early (H3) and delayed hypoxic preconditioned groups (H6). Co-immunoprecipitation and Western blot were applied to quantitatively analyze the phosphorylation levels of cPKCγ-interacting ERK1/2 in cytosolic and particulate fractions of hippocampus of HPC mice. Results ERK1/2 could be co-immunoprecipitated by cPKCγ in the hippocampus of mice. The phosphorylation levels of cPKCγ interacting ERK1/2 at tyrosine 204 decreased significantly in the hippocampus of H3 and H6 groups when compared with that of the H0 group (P<0.05). Conclusion cPKCγ could interact with ERK1/2 in the hippocampus of mice, and their interaction might be involved in the development of cerebral hypoxic preconditioning of mice.