The studies demonstrated that microemulsion system comprising Mirtazapine Capmul PG 8 (6.78% v/v), Tween 20 (31.64% v/v), PEG 400 (15.82% v/v) and distilled water (45.76% v/v) and mucoadhesive microemulsion system (0.5% HPMC K4 M based microemulsion) were optimal for intranasal delivery of Mirtazapine. The mucoadhesive microemulsion systems are transparent and stable at ambient temperature for 3 months. Results of nasal Ciliotoxicity study confirmed that developed mucoadhesive microemulsion containing Mirtazapine had no cilio toxicity. Enhanced rate and extent Mirtazapine release following application on excised nasal mucosa from Mirtazapine mucoadhesive microemulsion may help in decreasing the dose and possibly maximize the therapeutic index. The formulated Mirtazapine intranasal mucoadhesive microemulsion represents a safe and viable approach to achieving rapid-onset systemic drug levels and higher bioavailability through bypass of the liver metabolism for the management of depression.