Purpose: To formulate biodegradable chitosan microspheres loaded with famotidine to overcome the poor bioavailability and frequent dose administration of the drug.Methods: Chitosan microspheres were prepared by simple emulsification technique based on glutaraldehyde crosslinking. Various process and formulation variables such as speed of emulsification, crosslinking time, drug/polymer ratio, volume of cross linking agent and volume of surfactant were optimized. The microspheres were characterized for entrapment efficiency, drug loading, in vitro drug release, surface morphology, as well as by particle size analysis, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC).Results: The microspheres showed a smooth surface with a narrow particle size distribution (105 – 219 μm) and an entrapment efficiency of up to 73 %. They exhibited controlled drug release characteristics with 85.6 % of the drug released over a period of 24 h with an initial burst release of 26.9 % in the first 2 h. Drug release followed Higuchi release kinetics. FTIR and DSC data indicate that there was no drug interaction between the drug and polymer used.Conclusion: The chitosan microspheres could be further developed as a potential biodegradable carrier for oral controlled delivery of famotidine.Keywords: Chitosan microspheres, Crosslinking, Controlled delivery, Famotidine, Glutaraldehyde, Biodegradable.