Carbamazepine (CBZ) is the first choice anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. A simple, rapid and accurate method for determination of carbamazepine in rat plasma in presence of licorice has been developed by using High performance liquid chromatography. A mixture of 55 % of Water Contains (1 ml Triethylamine per 1 liter) and 45 % of Acetonitrile of pH of 6 (adjusted with phosphoric acid) was used as a mobile phase, BDS hypersil C18 column (150mm×4.6mm,i.d 5μ) and a flow rate of 1 ml/min were used, the auto-sampler injection volume was 15 μL, and metronidazole benzoate was used as internal standard. The retention time for carbamazepine and metronidazole benzoate were 2.8 and 3.7 minutes, respectively. The method was validated in terms of linearity (R2= 0.9997) for the concentration (80-4800) ng/ml, precision, accuracy, stability and recovery. A and B groups of rats (n = 8 for each group) were used in the preclinical study. The first group (A), carbamazepine was administrated with water. While in group B, licorice was given instead of drinking water and pre-administrated to the rates before giving carbamazepine dose (10mg/kg). Plasma levels of carbamazepine were compared with plasma levels of carbamazepine with licorice. The maximum plasma concentration (Cmax), area under curve (AUC) and time to reach maximum concentration for carbamazepine with water were (4129.66 ng/ml, 31860.95 ng*hr/ml, and 1.00 hr) respectively. They were significantly reduced in presence of licorice juice (2885.53 ng/ml and 15776.70 ng*hr/ml, 0.50 hr), p value <0.05. In conclusion, we advise to avoid the licorice intake with CBZ or Caution should be considered when licorice is given with carbamazepine, since licorice lower plasma level of carbamazepine when pre-administrated