Abstract: AIM To study the pharmacokinetics and relative bioavailability of salbutamol aerosol in healthy volunteers. METHODS An HPLC method for the determination of salbutamol in human plasma was improved. Ten healthy male subjects were enrolled. A randomized, two way crossover, open design was adopted. After the subjects inhaled or orally administered salbutamol, fourteen blood samples were taken at predetermined time. The concentrations of salbutamol in plasma were determined by HPLC, and then assessed with PCNONLIN software to obtain the pharmacokinetic parameters and relative bioavailability of aerosol versus water solution. RESULTS The standard curve was linear over the range 0.2-20 ng·mL^-1. The intra- and interassay RSDs were 7.01% and 2.10% at 0.4 ng·mL^-1, 2.18% and 5.25% at 4.0 ng·mL^-1 and 4.61% and 4.85% at 15.0 ng·mL^-1. The recoveries were between 90% and 110%. The pharmacokinetics of salbutamol aerosol was described well with a two-compartment model, and the parameters for salbutamol inhaled and orally administered were assessed as follows: T_max were (0.22±0.07) h and (1.8±0.6) h, C_max were (3.4±1.1) ng·mL^-1 and (3.9±1.4) ng·mL^-1, T_1/2 β were (4.5±1.5) h and (4.6±1.1) h, respectively. The AUC_{0-20 min (inhal)} was 7.94 times as high as the AUC_{0-20 min (po)}. There were significant differences between T_max, AUC, K₁₂, K₂₁, αand T_1/2 α (P<0.05). The relative bioavailability of salbutamol aerosol was 57.23% compared with its oral solution. CONCLUSION The assay was sensitive, specific, accurate and precise. The absorption process of salbutamol aerosol in human was significantly different from that of the oral solution. It was demonstrated that AUC_{0-20 min} reflected the lung availability of salbutamol inhaler.