The preparation of chitosan-tripolyphosphate (chitosan-TPP) particles by the spray drying had been reported word widely for a sustained release of drugs to prevent rapid drug metabolism. Although the spray drying is a straightforward procedure turning a liquid feed into a well-defined dry powder, seldom research works were focusing on how the processing parameters and liquid feeding constitutions of spray drying system might affect the properties of spray-dried chitosan particles loaded with drugs, such as the particle size and morphologies, which would be very important to drug encapsulation and dissolution of the drug delivery design. This study thus prepared the chitosan particles with theophylline (TH) loaded as a model drug and TPP as cross-linker at various spray drying conditions. Our results indicate the diameter of the TH/chitosan-TPP particles made by customized spray drying apparatus spans from 424 to 497 nm with a geometric standard deviation of less than 2. The corresponding release of TH was tunable by the chitosan-TPP matrix density under the selected spray drying temperature and the carrying air flow rate. These results suggest an indeed need for optimized spray drying processing conditions to make the ideal spray-dried TH/chitosan-TPP particles for the desired drug delivery.