The invention discloses an isoniazide and rifampicin co-loaded microsphere sustained release preparation and a preparation method thereof, two antituberculous drugs, isoniazide and rifampicin, are jointly entrapped in PLGA microspheres by using an electrostatic fluid spraying technology, the average particle size of the microspheres meets the effective particle size of pulmonary administration, and the entrapment efficiency is high. A 15-day in-vitro drug release experiment shows that the cumulative drug release rate of the drug in the microspheres is 40%-60%, and the technical requirement of slow release is met. The local drug concentration of tuberculosis drugs in the lung can be effectively improved, the administration frequency is reduced, toxic and side effects are reduced, and the economic benefit ratio of the drugs is improved.