Objective  To investigate the ultrastructural changes of hippocampus in urea transporter B (UT-B) null mice and the alterations of distribution and expression level of aquaporin 4（AQP4）in brain, and to discuss the relationship between AQP4 expression changes and depression-like behaviors in UT-B null mice.   Methods  Behavior differences of wild-type and UT-B null mice（10 in each group） were detected with sucrose preference and forced swimming test. The ultrastructural changes of hippocampus were observed by transmission electron microscopy (TEM). Immunohistochemistry and Western blotting were performed to detect the distribution and expression level of AQP4 in both genotypes.   Results  The sucrose preference index of wild-type mice and UT-B null mice were (84.67±1.62)% and (65.67±2.66)%, respectively (P<0.001). The immobility time of forced swimming was (209.1±7.00) seconds and (128.6±3.75) seconds respectively (P<0.001). The two behavioral test results showed that UT-B null mice exhibited depression-like behavior. TEM results displayed the abnormal neurons with swelling of myelinated and unmyelinated fibers and degenerative changes, and perivascular astrocyte endfeet swelling. Immunohistochemistry results showed AQP4-immunoreactive (IR) cells were significantly reduced in cortex, hippocampus and thalamus. AQP4-IR cells were distributed in the pia matter, ependymal and cerebrovascular, but the perivascular immunostaining decreased. Western blotting analysis showed that the expression level of AQP4 in hippocampus was down-regulated by 27.1% (P<0.05).   Conclusion  Reduced expression of AQP4 in the cerebral cortex and hippocampus of UT-B null mice might induce depressive behaviors by inference neurogenesis and cerebral metabolism.