Objectives: The aim of this study is to compare the effect of honey 12.5% and chlorhexidine 0.2% mouthwashes to reduce the oropharyngeal bacterial colonization in mechanically ventilated patients in ICU. Design: This study is a phase III randomized, controlled clinical trial with two groups will be compared. 60 patients newly admitted to internal and trauma ICU of two medical, Educational and therapeutic centers of Sanandaj city related to Kurdistan University of Medical Sciences (KUMS) will be selected by convenience sampling and then will be allocated in two groups of 30 patients using random blocks module. Inclusion criteria: New patients admitted to the ICU with an endotracheal tube intubation and mechanical ventilation undergo less than 12 hours previously, and have at least 4 days of mechanical ventilation. Exclusion criteria: Patients with systemic infections, lung cancer, thrombocytopenia or other coagulopathies, diagnosed immunosuppressive disease, known allergy to chlorhexidine, honey and other complications of mouthwash solutions used in this study, leukopenia, having obvious symptoms of aspiration, pregnancy, organ transplants, oral mucositis, high blood sugar, oromaxillofacial surgery and extensive burns. Interventions: In both groups, mouthwash will be applied twice a day (8 am- 8 pm) until four days by two trained nurses using sterile technique. Honey mouthwash used in this study is native honey from Zagros Mountains of Kurdistan in west of Iran and is prepared by thyme and astragalus herbs. After confirming the honey in the laboratory of Kurdistan Agriculture Institution, honey mouthwash 12.5% will be prepared on a daily basis using sterile technique. Also, the solution of chlorhexidine 0.2% with commercial name Hexodyne used in this study is produced by World Health Co. with license no.44.13186 and approved by the ministry of health and the medical education of Iran. Main outcome measures: Swab samples will be taken from the mouth and throat of all patients three times (before the intervention, 48 h and 96 h after the intervention), and will be transferred onto the Sheep' Blood Agar and Eosin Methylene Blue (EMB) Agar culture plates ,and after 24-48 hours plates will be investigated for bacterial growth and colonization. In cases of colonization, the biochemistry and morphologic tests will be used to determine pathogenic microorganisms.