The Box-Behnken experimental design and response surface methodology were employed to optimize the preparation of the aspirin micro-porous osmotic pump tablets. The core of the tablet was prepared with aspirin and β-CD inclusion, then osmotic pump tablets were obtained by coating a layer of cellulose acetate containing PEG 4000 as porogenic agent. The in vitro release test shows that the aspirin inclusion complex microporous osmotic pump tablets prepared by this process has a cumulative release rate of 1.5% and 1.6% within 0~2 h in artificial gastric juice compared to commercially available aspirin enteric coated tablets. After adjusting the release medium to pH 6.8, there is no significant difference in the cumulative drug release between the two formulations at 10 h. And the inclusion complex microporous osmotic pump tablet shows zero order release and complete release within 12 h(cumulative release rate > 90%), indicating the possibility of reducing drug damage to the gastric mucosa.