Lithium (Li) therapy has widely used in the treatment of bipolar disorder. Consequently, consciousness of the
side effects and pathogenesis of this metal is needed for such treatments. Recently, information on the interaction
of Li with oxidative markers and organs toxicity attend the researchers over the world. In the present study we
have tried to evaluate the influence of oral administration of LiCl for 4 weeks on the oxidative stress marker and
histological structure of brain in male rats. Fifty adult male albino rats weighing 135±15 gm was categorized into
5 groups (10 rats each). Group I worked as negative control, group II administrated with LiCl (0.20 mg/kg bw)
in drinking water, group III, IV and V were administrated with Zn (10 mg/kg bw), VE (100 mg/kg bw) and their
combination twice a week besides the daily administration of LiCl for 4 weeks, respectively. Rats after
anesthesia with ether killed for collocation of brain for histopathological and biochemical analysis. Data obtained
showed a significant increase in LPO, NO, GSH and Li content and the activities of SOD, CAT and AChE with
demylination of the nerve fibers and degeneration of neurons in brain of LiCl treated rats. Co-treatment of ratswith Zn or VE results in a significant decrease in LPO, NO, GSH content in the activities of SOD, CAT and AChE with less or normal structure of the brain. However, co-treatment with combination of Zn and VE caused a significant increase in SOD, CAT and AChE activities with normal histological structure.In conclusion, the data from the present study show that Zn and VE and their interaction are effective in protection against Liinduced
brain toxicity in rat with priority for the combination.