Abstract: The objective of this study was to prepare the chitosanmicrocapsule of doxycycline hyclate by emulsifying crosslinking method, and evaluate its surface morphology, particle size, drug encapsulation efficiency, in vitrorelease et al. Doxycycline hyclate solution and microcapsule suspension were orally administrated on health rabbits to study the pharmacokinetic of doxycycline hyclate microcapsule. Six rabbits received single doses of doxycycline hyclate solution at 20 mg·kg-1, and the other six rabbits received doxycycline hyclate suspension at the same doses. The plasma concentration of doxycycline hyclate was determined by HPLC. The stationary phase was C18, and acetonitrilemethanol0.01 mol·L-1 oxalic acid solution (2:1:7) was taken as the mobile phase, AUV detector was used at 346 nm. Using doxycycline hyclate solution as a reference, their pharmacokinetic differences were compared. The results indicated that the microcapsule was successfully prepared. SEM observation showed the drugloaded microparticles exhibited spherelike shape and small particle size was about 10 μm. The mean content and encapsulation efficiency were 20.60% and 85.54%, respectively; In vitro release studies revealed that the drugloaded microparticles substantially enhanced the release property. The pharmacokinetic data of two groups was in line with a twocompartment model. The main pharmacokinetic parameters were shown as Cmax of (1.74±0.00) vs. (1.10±0.00) mg·L-1, Tmax of 3 vs.12 h, T1/2α of (1.16±0.53) vs. (7.51±2.87) h，T1/2β of (2.19±0.38) vs. (9.00±1.60) h，and AUC(0t) of (11.71±0.17) vs. (32.51±0.20) mg·L-1·h, respectively. The relative bioavailability of the microcapsule was 289.4%. It resulted that doxycycline hyclate microcapsule exhibited high bioavailability and was slowly absorbed and distributed after administration in the healthy rabbit.