Depression is one of the most common psychiatric disorders. Chronic inflammatory response has been viewed as a key factor in depression. Acupuncture in Chinese medicine has been shown to be an effective treatment for depression. In the present study, we investigated the mechanism underlying antidepressant effect of acupuncture. The rats were subjected to chronic unpredictable mild stress (CUMS) for 28 days to induce depressive-like behaviors. Acupuncture treatment was applied once every other day during the 28-day stress period. The behavioral tests (body weight, sucrose consumption and locomotor activity) were performed. The expressions of nitric oxide (NO), prostaglandin E-2 (PGE(2)), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-B-K) were determined in the rat hippocampus and prefrontal cortex. CUMS induced depressive-like behavior in rats, which was alleviated by acupuncture treatment. The increased levels of NO, PGE(2), iNOS and COX-2 induced by CUMS, were all significantly decreased in the hippocampus and prefrontal cortex by acupuncture. Moreover, acupuncture markedly inhibited the activation of NF-B-K in rats. These findings showed that the antidepressant-like effect of acupuncture might be mediated by inhibition of inflammatory mediators via modulation of NF-kappa B in the brain regions. (C) 2016 Elsevier Inc. All rights reserved.