Tilmicosin (TMS) is an important antibiotic in veterinary medicine, but its extreme bitter taste limits its use. In this study, TMS was encapsulated in octenyl succinic anhydride modified starch/maltodextrin (HI-CAP/MD) composite capsules with a spray drying method. The TMS microcapsules (TMS-MC) exhibited good drug loading performance with drug loading (DL) and encapsulation efficiency (EE) of 9.90 ± 0.23 % and 98.03 ± 1.56 %, respectively. There was no significant change in particle diameter and zeta potential for the emulsion and redissolved TMS-MC. These results combined with FT-IR, TGA and DSC showed the crystalline shape and chemical structure of TMS did not change during the microencapsulation. In vitro release characterization in an acidic medium (pH 1.2) and an alkaline medium (phosphate buffered solution, pH 6.8) showed that TMS-MC can be rapidly released in vitro. The bitterness evaluation implied the bitterness of TMS was masked after microencapsulation. In vitro bacterial inhibition test showed the bacterial inhibitory activity of TMS was not reduced by the microencapsulation, but was much better than that of the commercially available tylosin (TLS). Therefore, HI-CAP/MD can effectively encapsulate TMS, mask the bitter taste and maintain a good bacterial inhibitory effect, making a new drug formulation with good development prospects.