Aims: To prepare solid lipid nanopaticles (SLNs) of Ketoprofen (KP) using microwave method. Ketoprofen (KP) is 2-(3-benzolphenyl) propionic acid with anti-inflammatory, analgesic and antipyretic property. The drug has a short half-life of 120 mins. It belongs to BCS Class II drug. Gastric irritation is a major limitation for delivery because of acidic nature of the drug. The development of solid lipid nanoparticles with its transdermal drug delivery was the aim of the present work. Methods: Microwave-assisted microemulsion technique was used for the development of solid lipid nanoparticles. Stearic acid was used as lipid and tween 80 was used as a surfactant. By vary-ing the type of lipid and input energy watt, batches were formulated. SLNs were evaluated for zeta potential, drug entrapment, particle size and in-vitro drug release. Crystallinity behaviour was deter-mined by differential scanning calorimetry and powder X-ray diffraction. Anti-inflammatory activity was evaluated for batch M4 of SLNs. The gel was prepared for M4 batch. It was evaluated for viscosity, pH, drug content, in-vitro and ex-vivo diffusion study. Results: SLNs were developed successfully. Based on the size, entrapment efficiency, stability and drug release, batch M4 was selected. SLNs showed 74.8% entrapment efficiency. Forty-fold im-provement was observed in the solubility. The particle size was 682.9 nm and average size 1047 nm. PDI was 0.685 and zeta potential was-29.5 mV. M4 SLNs batch of gel showed burst release followed by a controlled release for 8 hrs in in-vitro drug release. Conclusion: SLNs were successfully prepared by Microwave-assisted microemulsion technique. SLNs with anti-inflammatory activity were successfully developed with their transdermal delivery. © 2021 Bentham Science Publishers.