Objective To investigate the effect of hippocampal brain derived neurotrophic factor precursor (proBDNF) in cognitive dysfuction induced by social isolation.   Methods Thirty C57BL/6 J male mice (4-week old) were randomly divided into group house (GH，n=15) and socially isolated (SI，n=15) groups. The GH group (5 mice/cage) and SI group (1 mice/cage) were reared separately under the same conditions. The novel object recognition test and the novel place recognition test were used to evaluate the cognitive function. The expression of BDNF mRNA in the hippocampus was detected by Real-time PCR. The expression of BDNF and proBDNF in hippocampus was detected by Western blotting. Matrix metallopeptidase-9 (MMP-9) and tissue plasminogen activator (tPA) were extracellular enzymes that catalyzed the transformation of proBDNF into mature BDNF. Expression of MMP-9 and tPA mRNA in the hippocampus were detected by Real-time PCR.   Results Compared with the GH group, the SI group showed significantly reduced discrimination ratio in the novel object recognition test and novel place recognition test. The result  of Real-time PCR showed that there was no difference in the expression of BDNF mRNA between SI group and GH group. The result  of Western blotting showed that the expression level of proBDNF in the hippocampus of SI group increased significantly compared with the GH group (P<0.01),and no difference in BDNF expression was found between the two groups; Compared with the GH group, the BDNF/proBDNF ratio in the hippocampus of SI group decreased. In addition, the result  of Real-time PCR showed that the expression level of MMP-9 and tPA mRNA in the hippocampus of SI group decreased significantly compared with the GH group.   Conclusion The social isolation-induced cognitive dysfuction in mice may be related to the up-regulation of proBDNF in the hippocampus．