Sertraline and Fluoxetine, are selective serotonin reuptake inhibitors (SSRIs). They exhibit clinical efficacy comparable with classical tricyclic antidepressants, but are devoid of some of the adverse anticholinergic and cardiovascular effects commonly associated with these drugs [1]. Sertraline and Fluoxetine effective drugs in treatment of depression. However, the side effects and clinical response of these drugs are dependent on their concentration in biological samples including plasma and urine. Therefore, monitoring concentration of these drugs are helpful to improve the response and minimize the accurrence of side effects. In the present work, the method consists of air-assisted liquid-liquid microextraction (simple, rapid, sensitive, low cost, and environmentally friendly microextraction method) that coupled with High Performance Liquid Chromatography-Ultraviolet detection, to preconcentration, determination and analysis of Sertraline and Fluoxetine in biological samples [2]. To this aim, in this study a green microextraction method based on DLLME is developed, called air-assisted liquid-liquid microextraction (AALLME). In this method, biological or aqueous sample was transferred into a centrifuge tube with conical bottom. Extraction solvent was added and then the mixture was rapidly sucked into a glass syringe and then was injected into the tube via syringe needle. The extractant was settled down in the bottom of the centrifuge tube after centrifugation. Extractant was withdrawn and injected into the HPLC system for analysis. In order to decrease the toxicity and harmful effects of disperser solvents on operators and environment, air is replaced with disperser solvent. In this study, the effective parameters on extraction efficiency such as type and volume of extraction solvents, number of suction-injection cycle, salt addition and pH are investigated and optimized [3]. According to the test results, the AALLME-HPLC-UV method was successfully applied for e