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Objective: The nucleus accumbens (NAc) receive histaminergic neurons from tuberomammillary nuclei. There are reports indicating that central histamine systems are involved in many physiological behavioral processes, including anxiety. The aim of the present study was to assess whether the histaminergic system of the NAc is involved in anxiety-related behaviors. Methods:   Rats   were   anesthetized   with   intra-peritoneal   injection   of ketamine  hydrochloride,  plus  xylazine  and  then   were  placed  in  a stereotaxic  apparatus.  In  addition,  two  stainless-steel  cannuale  were placed 2 mm above the nucleus accumbens shell. Seven days after recovery from surgery, the behavioral testing was started.  As a model of anxiety, the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used in male Wistar rats. Results: Intra-NAc administration of histamine (0.01, 0.1 and 1 µg/rat) increased the percentage of open arm time (%OAT) and open arm entries (%OAE)  ,but  not  locomotor  activity,  indicating  an  anxiolytic  response. Furthermore, bilateral microinjections of different doses of the H1 receptor antagonist pyrilamine (0.001, 0.01, 0.1 and 1 µg/rat) or the H2  receptor antagonist ranitidine (0.001, 0.01, 0.1 and 1 µg/rat) into the NAc increased %OAT and %OAE , but not locomotor activity. However, both histamine and histamine receptor antagonists showed an anxiolytic-like effect ; the antagonists (1 µg/rat) also decreased the histamine response. Conclusion: The results may indicate a modulatory effect for the H1  and H2  histamine receptors of nucleus accumbens in the anxiety behavior of rats.