The objective of this work was to improve the solubility and enhance the antimicrobial activity of apoorly water soluble drug Clotrimazole (CLT) via formulating it as microemulsion systems. Microemulsions with varying mass ratios (Km) of surfactant and co-surfactants (Km 0.5/1, 1/1, 2/1) were prepared using Isopropylpalmitate (IPP) as oil phase, poly sorbate 80 (Tween 80) as surfactant, n-butanol as co-surfactant and distilled water as a aqueous phase. The area of o/w microemulsion region in pseudoternary phase diagram was increased with increasing ratio of Tween 80 to n-butanol. The solubility of CLT in microemulsion reached the maximum at Km 1/1 mixture of Tween 80 and n-butanol, the solubility value of CLT increased to 4100-fold, respectively to that of water. The release rate of CLT from microemulsion systems and also the antimicrobial activity reached the maximum with 0.5/1 Km.