OBJECTIVE： To establish the method for the content determination of risperidone （RIS） in cerebral tissues of rats. METHODS： Rats were given RIS suspension 30 mg/kg， ig， and sacrificed 30 min later to separate cerebral tissue. The concentration of RIS in cerebral tissues of rats was determined by HPLC system with UV detector using berberine hydrochloride as internal standard. The chromatographic conditions were that Wondasil C18 column （250 mm×4.6 mm， 5 μm） was used with mobile phase consisted of acetonitrile-0.01 mol/L ammonium acetate （50 ∶ 50， V/V） at the flow rate of 1.0 ml/min； the detection wavelength was set at 280 nm； the column temperature was maintained at room temperature， and sample size was 25 μl. RESULTS： There was a good linear relationship of RIS concentration in cerebral tissues of rats within the range of 0.2-27.0 μg/ml （r＝0.999 9）. The method recovery was from 97.28％ to 109.10％ and extraction recovery was from 94.59％ to 97.48％（n＝5）； intra-day and inter-day RSDs were both below 5％ （n＝5）. The limit of quantitation was 0.5 μg/ml. The content of RIS in cerebral tissue of rats was （3.48±0.50） μg/g （RSD＝14.7％， n＝6）. CONCLUSIONS： The established method is simple， rapid， sensitive and accurate for the content determination of RIS in cerebral tissues of rats.