Abstract: AIM: To study the pharmacokinetics of harmine (HAR) intravenous emulsion in rats and mice. METHODS: The pharmacokinetics of the emulsion and solution containing harmine were compared in rats by cross-over test. The drug concentration was determined by HPLC. ³H was labelled in harmine, and the emulsion and solution of ³H-HAR were prepared. The radioactivity (Bq) of the various organs and blood were detected by liquid scintillation counting. RESULTS: The concentration-time curves for both the emulsion and the solution fit three compartments open model after intravenous injection to rats. The volume of distribution(Vc), clearance(Cl) and the mean residence time(MRT) revealed significant differences between the emulsion and the solution, suggesting that the emulsion showed stronger tissue distributing ability than the solution. Meanwhile, lower radioactivity plasma concentration was found after iv injection of the emulsion to the rats, indicating that the drug delivery system may have other transport ways except blood transport. The distribution of emulsion in the tissue of mice showed that there were definite direction and accumulation in the lymph system. CONCLUSION: The intravenous emulsion, as drug delivery system, may enhance the drug quantity in targetted organs and prevent the drug from transporing to brain, so that the emulsion form can effectively reduce the toxicity and adverse effects of harmine. This conclusion was also evident from the results of LD₅₀ determination.