〔Abstract〕 Objective To investigate the effects of curcumin(CUR) on lipopolysaccharide(LPS)-induced depression in mice and its mechanism. Methods Thirty male ICR mice were randomly divided into control group, LPS group and CUR group, ten mice in each group. The depression model was established by intraperitoneal injection of LPS 1 mg/kg. The depressive-like behaviors of mice were evaluated by sucrose preference test(SPT), open field test(OFT) and forced swim test(FST). The changes of Nissl body in neurons of prefrontal cortex(PFC) were observed by Nissl staining. C-Jun N-terminal kinase(JNK), phosphorylated JNK, Bax(Bcl-2 associated X protein), Bcl-2, caspase-3 in PFC area were detected by Western blot. Results The percentage of sweet water preference, total distance in OFT and crossing number in CUR group were higher than those in LPS group(P<0.05), and immobility time in FST was lower than that in LPS group(P<0.05). The results of Nissl staining showed that number of nerve cells in CUR group was more than that in LPS group(P<0.05).Western blot showed that the expression levels of p-JNK, Bax and caspase-3 were decreased in PFC area of CUR group while Bcl-2 were increased compared with the LPS group(P<0.05). Conclusion Curcumin can improve the depressive behavior induced by LPS and reduce the damage of neurons, which may be related to the inhibition of JNK phosphorylation, the decrease of Bax and Caspase-3, and the increase of Bcl-2 expression.