In current research, Posaconazole-loaded solid lipid nanoparticles (SLNs) were prepared using glyceryl monostearate (GMS) as a lipid by hot homogenisation method. Posaconazole was selected as a model drug for BCS (Biopharmaceutics Classification system) Class II drugs. Solubility is a major concern for the improvement of oral bioavailability for poorly water soluble drugs as in case of BCS class II. The SLN batches were optimized based on average particle size, drug entrapment efficiency, drug loading and percentage yield. The optimized SLN composition was characterized in terms of particle shape and size, drug entrapment efficiency and drug loading. In-vivo antifungal activity against Microsporum canis for optimized batch was carried out using albino rat model for the treatment of dermatophytosis. The bioavailability of drug after oral administration in albino rats was found to be significantly higher as compared to the conventional dosage form of drug. A complete mycological and clinical cure was observed during the study in M. canis infected albino rats. Posaconazole loaded SLNs were administered orally once daily in infected rats for 7 days. It can be concluded from our study that SLNs improves the oral delivery of poorly water soluble drugs like Posaconazole that belongs to BCS Class II drugs.