This study aims to investigate the potential of solid lipid microparticles (MP) and hybrid polymer-lipid MPs for sustained delivery of a peptide drug, leuprolide. A peptide-phospholipid complex was prepared to increase the compatibility of the peptide with triglyceride (TG) and poly (lactide-co-glycolide) (PLGA). Peptide loaded solid lipid MPs, PLGA MPs, and hybrid MPs were prepared using a spray drying method and characterized in terms of particle size, morphology and encapsulation efficiency. The pharmacokinetics and pharmacodynamics of leuprolide after subcutaneous injection of spray-dried MPs were evaluated in rats. Spray-dried MPs were spherical ranging in size from 4 μm to 10 μm, which are suitable for injection. After subcutaneous administration of reconstituted MPs, leuprolide could be detected in plasma samples of rats for one to two months, depending on the formulation and dose. Sustained release of leuprolide from PLGA MPs and glyceryl tristearate (TG18) MPs was observed over one month, with a chemical castration effect of 25 and 30 days, respectively. The bioavailability of leuprolide from PLGA-TG18 hybrid MPs was approximately four times higher than that from TG18 MP and PLGA MP alone using the same dose of leuprolide (6 mg/kg). Chemical castration in rats was observed over 30 and 60 days after injection of the PLGA-TG18 hybrid MP with a dose of 3 mg/kg and 6 mg/kg leuprolide, respectively. Additionally, a much lower Cmax was observed for the hybrid MP group. In conclusion, spray-dried PLGA-triglyceride hybrid MPs can be used as better carriers than other MPs for subcutaneous delivery of peptide drugs due to the synergetic effect of lipids and PLGA for sustained drug release from the spray-dried MP.