The objective of this work was to prepare and evaluate ketoprofen-loaded albumin microspheres for intramuscular administration. Microspheres were prepared by emulsion cross-linking method using a 2(3) factorial design and the effect of different factors on entrapment efficiency was determined. Microspheres were evaluated for entrapment efficiency, percentage yield, particle size and release behaviour. Selected formulations were then tested by differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Further they were analysed for residual solvents, syringeability and stability. Microspheres were then sterilized and bioavailability studies were carried out in New Zealand white rabbits. The physical characteristics of microspheres showed that they were suitable for IM administration. The sterilization technique adopted was adequate to maintain sterility. In vivo studies showed increase in C(max), AUC, t(1/2) and MRT (p < 0.05) administered in the form of microspheres. MRT of ketoprofen was almost 3.2-times in the form of microspheres. From these results it was concluded that the developed albumin microspheres of ketoprofen is a potential delivery system for once-a-day intramuscular administration.