Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe hospital-acquired infections, especially in immune-compromised hosts. P. aeruginosa is notorious for its resistance to antibiotics. Exoenzyme S is one of the several toxins involved in Spreading of infections in burns. It’s been revealed that deletion of genes encoding the components of exoS, in wild-type P. aeruginosa, confers hyper susceptibility to anti phagocytic agents. Antimicrobial and antifungal properties of some herbal medicines were numerously reported. In this study the effect of Satureja khuzestanica extract, an endemic plant of Iran, on the expression level of exoS gene in P. aeruginosa were investigated. For this purpose, MIC was determined for P. aeruginosa. Then, bacteria were treated with S. khuzistanica extract. ExoS and gyrA genes expression in treated and non-treated bacteria, before and after expose was evaluated using RT-PCR technique. Surprisingly, the expression level of exoS gene was decreased in the presence of S. Khuzestanica. However, the expression of gyrA gene that was used as an internal control was not altered before and after treatment with this herb. Based on the results, S. Khuzestanica could play a, major role in lowering the P. aeruginosa resistance to drugs, by reducing exoS gene expression. According to results of current research we hope in future be used it to the clinic with a wider range as a complementary therapy and also for surgery operation and etc.