Objective To study the effect of hypothalamus pituitary adrenal(HPA) axis disorder on the hippocampal formation in rats with anxious depression and to explore its potential pathogenesis. Methods Rats were randomly divided into control group, vehicle group, anxiety group, depression group and anxious depression group with 12 rats in each group. Anxious depression rats were intervened by chronic restraint stress combined with corticosterone injection for continuous 21 d. Then, elevated plus maze (EPM), open field test (OFT), forced swimming test(FST)were used to evaluate the anxious and depression like behavior in rats, HE staining to check pathological changes of the HPA axis tissue and hippocampus. The plasma levels of CRH, ACTH and CORT of rats were detected by ELISA, and the expression of GR in hippocampus was detected by Western blot. Results Compared with control group and depression group, there were significant differences (P<0.01 or P<0.05) in OE% and OT% at EPM and independent activity frequency during OFT, which was similar to anxious depression group. Compared with control group and anxious group, the immobility time in FST was increased significantly (P<0.01). HE staining showed that all tissues of HPA axis were damaged, and the hippocampal neurons were swollen and vacuolated. ConclusionsAnsious depression rats have significant anxious and depressive behaviors, its pathogenesis may be closely related to the HPA axis disorder and hippocampus region damage.