Objectives: The present work was designed to studythe role of endocannabinoid system in the obesity associated atherogenesis and trying to clarify its possible mechanism/s of action. Methods: Thirty adult male wistar albino rats were utilized in the present experiment. They were divided into three equal groups (10 rats each); Group 1: Lean control group, which were fed normal laboratory chow diet and gavaged once daily by dimethyl sulfoxide in a dose of 0.6ml/kg /day for 10 weeks. Group 2: Atherogenic diet group which were fed high fat diet and gavaged once daily by dimethyl sulfoxide as group 1. Group 3: Atherogenic diet treated group which were fed high fat diet and gavaged once daily by NIDA-41020 (a selective cannabinoid receptor 1 blocker) in a dose of 10mg/ kg /day for 10 weeks. Then body mass index (BMI), bleeding time, and total clotting time were assessed. After that, the animals were sacrificed and lipid profile, atherogenic index, bleeding time, platelet aggregation percentage, clot retractions, clotting time, prothrombin time (PT), activated partial thromboplastin time (aPTT), total & differential leukocytic counts and serum adiponectin levels were assessed in all groups. The aorta was obtained from each animal dissected and stained by haematoxylin/eosin and oil Red O staining for histological examination and detection of aortic thickness and foam cells deposition. Results: The laboratory investigations and histological examination revealed, significant increases in BMI, lipid profile, atherogenic index, platelet aggregation%, peripheral monocytic count, and aortic thickness in the high fat diet received group versus lean controls which were otherwise associated with significant decreases in total clotting time, PT, aPTT, serum HDL & adiponectin levels. These changes were significantly and profoundly inhibited by the administration of the cannabinoid receptor antagonist. Conclusion: The endocannabinoid system is involved in the atherogenic changes associated with obesity. These effects were attributed to interference with serum adiponectin level, dyslipidemia, hypercoagulability, increased platelet activation & peripheral as well as endothelial recruitment of monocytes. These effects were found to be via activation of cannabinoid 1 receptor.