Abstract: OBJECTIVE To prepare tetrahydropalmatine(THP) gastric floating microsphere and investigate in vitro release characteristics and flotation performance of THP gastric floating microsphere in different conditions. METHODS Prepared THP gastric floating microsphere by emulsion-solvent diffusion method. The flotation performance of THP gastric floating microsphere was investigated by direct observation in the release medium of 0.1 mol·L^-1 hydrochloric acid solution, pH 3.0 PBS, pH 4.5 acetic acid buffer, and pH 6.8 PBS, and under different speeds in 50, 100, 150 r·min^-1, which was simulated gastrointestinal tract environment. To investigate in vitro release characteristics of THP gastric floating microsphere by rotating basket method of the above release conditions. Taking the rotundine tablets as reference, compared their release behavior in vitro in evaluated gastric acid environment. RESULTS In the different release conditions, THP gastric floating microsphere could immediately float 12 h, its floating rate was 100%. The accumulative release rate after 12 h in the different release medium were (90.55±4.65)%, (81.48±5.92)%, (66.24±3.00)%, (51.93±2.35)%, and in the different speeds were (84.26±3.22)%, (90.55±4.65)%, (94.70±2.15)%. The accumulative release rate of the rotundine tablets was (78.31±11.01)% in 0.5 h in the gastric acid environment (0.1 mol·L^-1 hydrochloric acid solution), and almost finished in 2 h. Meanwhile, THP gastric floating microspheres had a good in vitro floating performance and sustained release effect, and finished release totally without phenomenon of sudden release. CONCLUSION THP gastric floating microspheres has a good in vitro floating performance and sustained release effect. Its in vitro release behavior conforms to the Higuchi equation.