Background: Diazepam is a synthetic benzodiazepine used for the treatment of anxiety and insomnia. It is a positive modulator of GABA A-receptors and facilitates neurotransmission of GABA, the major inhibitory neurotransmitter in CNS. It has been found that between 27% and 45% of patients prescribed diazepam or lorazepam for an average 3, 5 years suffered withdrawal symptoms, curcumin has been indicated to inhibit the prostaglandin syntheses on of endogenous agent substrate shown to facilitate the action of psyco-action agent including diazepam. curcumin is most likely mediated through its ability to inhibit cyclooxygenase-2 (COX-2) which catalyze the arachidonic acid to prostaglandin which function to promote the inflammation. This study was aimed to indicate the effect of curcumin on the anxiolytic action of diazepam in animal model. Method: The experiments were carried out on male mice divided to six group, control group was given diazepam 10mg , normal group was given CMC only, treatment group was given diclofenac 5mg , and three other groups were given curcumin (2.5, 5, and 10 mg/kg) respectively. Measurement behavior of the mice with elevated plus maze, and acetylcholine esterase (AChE) activity was conducted for each group. Result: the administration of curcumin 5 mg/kg and 10 mg/kg significantly reduce the effect of diazepam (p < 0.005), while the curcumin 2.5 mg/kg showed no significant effect. Conclusion: administration low dose of curcumin showed the same effect on behavior as that after diazepam, while after high dose of curcumin significant difference in behavior was observed. Result suggest that curcumin block the effect of diazepam.