Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disability that demonstrates impaired social interactions, social communication deficits, and restrictive/repetitive behaviors. It is reported that children with ASD and some animal models of ASD show the abnormality of endocannabinoid (eCB) systems. To determine the causal role of the eCB systems in the ASD, we have investigated the relationship between the eCB system and ASD-like symptoms, using the cannabinoid CB₁ receptor knockout (CB1KO) mice. We found that male CB1KO mice demonstrated reduced sociability (3-chambered social approach task) and elevated repetitive grooming behaviors (hole-board test). Moreover, CB1KO mice showed resistance to change a learned pattern of behavior (reversal learning task using T-maze). On the other hands, the serum oxytocin, reported as lower levels in autistic children, significantly decreased in CB1KO mice. These findings suggest that CB1KO mice show abnormal behavioral phenotypes and endocrine system including social deficits, repetitive behaviors, cognitive inflexibility and low serum oxytocin levels, which have face and construct validity as an animal model for ASD. Therefore, the CB1KO mice will be a valuable tool for the exploration of pathological mechanisms and development of novel therapeutics in the ASD.