Aim:To determine the uptake extent of Huperzine A(Hup A)into the brain afterintranasal administration of Hup A in situ gel to rats,and to compare the pharma-cokinetic parameters between intranasal administration and iv and po.Methods:Hup A was administered to male Sprague-Dawley rats via nasal,iv and oral routesat the dose of 166.7,166.7,and 500 μg/kg,respectively.Blood and brain tissuesamples including the cerebrum,hippocampus,cerebellum and olfactory bulbwere collected,and the concentrations of Hup A in the samples were assayed byHPLC.The area under the concentration-time curve(AUC_0→6 h)and the ratio ofthe AUC_brain to the AUC_plasma(drug targeting efficiency,DTE)were calculated toevaluate the brain targeting efficiency of the drug via 3 administration routes.Results:The AUC_0→6 h of the drug in the cerebrum,hippocampus,cerebellum,left olfactory bulb and right olfactory bulb after intranasal administration of theHup A in situ gel were 1.5,1.3,1.0,1.2,and 1.0 times of those after iv administrationof the injection,and 2.7,2.2,1.9,3.1,and 2.6 times of those after administration ofthe oral formulation.The AUC_brain0→6 h/AUC_plasma0→6 h of HupAin the cerebrum,hippocampus and left olfactory bulb following the intranasal administration dosewere significantly higher(P<0.05)than the iv dose.Conclusion:Intranasal deliv-ery showed a viable,non-invasive strategy for delivering the drug into brain. Aim: To determine the uptake extent of Huperzine A (Hup A) into the brain afterintranasal administration of Hup A in situ gel to rats, and to compare the pharma-cokinetic parameters between intranasal administration and iv and po. Methods: Hup A was administered to male Sprague-Dawley rats via nasal, iv and oral routesat the dose of 166.7, 166.7, and 500 μg / kg, respectively. Blood and brain tissues samples including the cerebrum, hippocampus, cerebellum and olfactory bulbs collected, and the concentrations of Hup A in the samples were assayed by HPLC. The area under the concentration-time curve (AUC_0 → 6 h) and the ratio of the AUC_brain to the AUC_plasma (drug targeting efficiency, DTE) were calculated to evaluate the brain targeting efficiency of the drug via 3 administration routes Results: The AUC_0 → 6 h of the drug in the cerebrum, hippocampus, cerebellum, left olfactory bulb and right olfactory bulb after intranasal administration of the Hup A in situ gel were 1.5, 1.3, 1.0, 1.2, and 1.0 times of those afte r iv administration of the injection, and 2.7, 2.2, 1.9, 3.1, and 2.6 times of those after administration of the oral formulation. AUC_brain0 → 6 h / AUC_plasma0 → 6 h of HupA in the cerebrum, hippocampus and left olfactory bulb following the intranasal administration dosewere significantly higher (P <0.05) than the iv dose. Conclusion: Intranasal deliv-ery showed a viable, non-invasive strategy for delivering the drug into brain.