Objective To investigate whether ketamine ameliorates the anxiety and depression symptoms of post‑traumatic stress disorder (PTSD) and the underlying mechanism. Methods Forty‑eight male C57BL/6 mice, aged 6‒8 weeks, were divided into the following four groups (n=12) using the random number table method: control+NaCl group (group CN), control+ketamine group (group CK), PTSD+NaCl group (group PN), and PTSD+ketamine group (group PK). PTSD animal model was established by inescapable foot shock (IFS) procedure. In groups CK and PK, mice were treated with ketamine 2.5 mg/kg by intraperitoneal injection beginning at 30 min after the IFS procedure, once a day for 14 d. Open field and elevated plus maze tests were performed on these mice at 15 d and 16 d after IFS procedures, respectively. Rats were euthanized at day 17 after IFS procedures to collect the brain. Quantitative real time polymerase chain reaction was used to detect the hippocampal brain derived neurotrophic factor (BDNF) mRNA levels and Golgi staining was used to detect the density of dendritic spine in pyramid neurons. Results In the open field test, no significant difference was observed in the distance travelled among the four groups (P>0.05). Compared with group CN, the mice in group PN showed decreased time spent in the center of the arena (P<0.05), less entries and time spent in the open arms in the elevated plus maze test (P<0.05), decreased hippocampal BDNF mRNA levels and dendritic spine density in pyramid neurons (P<0.05). Compared with group PN, the mice in group PK showed an increased time spent in the center of the arena, more entries and time spent in the open arms (P<0.05), increased hippocampal BDNF mRNA levels and dendritic spine density in pyramid neurons (P<0.05). Conclusions PTSD model mice exhibited obvious anxiety and depression‑like behaviors, which may be related to the decrease of BDNF mRNA levels and dendritic spine density in the hippocampus. Ketamine increased the expression of hippocampal BDNF mRNA levels and dendritic spine density, thereby alleviating anxiety and depression‑like symptoms in PTSD mice.