Introduction: Bipolar disorder is a severe mental illness characterized by alternating bouts of mania and depression.The pharmacotherapy of bipolar disorder includes a variety of drugs, however, nearly one third of bipolar patients suffer recurrent episodes of mania and depression and many suffer severe side effects.This underscores the urgent need to develop more efficacious and better-tolerated drugs.The mechanism(s) underlying the therapeutic effects of anti-bipolar drugs is not fully understood.Accumulating evidence suggests that inflammation plays a role in the pathogenesis of bipolar disorder and, consistently, mood-modulating drugs were shown to exhibit anti-inflammatory properties.The atypical antipsychotic olanzapine (OLZ) has been shown to confer mood-stabilizing effects in a number of clinical trials.Aim: The aim of this research was to examine the effects of OLZ on lipopolysaccharide (LPS)-induced inflammation in rat primary giia cultures.Methods: Glia cells are the major source of inflammatory mediators production in the brain.Thus, as a model system, primary glia cells are highly relevant to the study of bipolar disorder.OLZ (1 or 10 M) was added to the culture medium at 6 (acute treatment) and 72 (chronic treatment) hours before addition of LPS.Cells were then exposed to LPS for another 18 hours.LPS was given at a concentration of 100 ng/ml.Cytokines levels were measured by ELISA and nitric oxide (NO) level was determined utilizing the Griess reaction assay.Results: Treatment with OLZ significantly altered LPS-induced secretion of inflammatory mediators, including tumor necrosis factor-, interleukin-10 and NO.Overall, OLZ treatment (acute and chronic) reduced the inflammatory response induced by LPS.These preliminary results suggest that OLZ has anti-inflammatory effects.Further study is necessary to unravel the mechanisms by which OLZ regulates inflammatory processes of the brain.