Biodegradable gemifloxacin microparticles were prepared to eradicate the resistant type pneumonia. For preparation of microparticles different techniques (solvent evaporation, solvent-evaporation crosslinking, double emulsion and spray drying) were used and compared. The process of spray drying using poly(d,l-lactic co-glycolic)acid was choosen considering the particle size and percentage yield. The critical processes as well as product related parameters were identified by Quality by Design approach. Optimization of formulation was performed by Taguchi design using particle size, percentage yield and percentage encapsulation efficiency as dependent variable while drug to polymer ratio, aspirator rate, inlet temperature and flow rate as independent variable. Optimized formulation was evaluated for particle size, percentage yield, percentage entrapment efficiency, in-vitro diffusion study and aerodynamic behavior. Taguchi design suggest that the batch containing drug to polymer (2:1), aspirator rate(50), inlet temperature (65°C) and flow rate (10ml/min) gives highest encapsulation efficiency (84%) and lowest particle size (2.75µm). The DSC and FTIR study revealed that there was no significant interaction between drug and polymer. The result of diffusion study revealed that the optimized batch was released at a controlled rate. Overall, the proposed formulation can be explored for inhalation route by the patient to achieve better targeting in deeper parts of lungs