Objective To observe the expression of endogenous cannabinoid receptor l (CB1) in rats with non-alcoholic fatty liver disease (NAFLD) and to preliminarily investigate the role of CB1 receptors in the pathogenesis of NAFLD. Methods Forty-eight male SD rats were randomly divided into three groups: control group (receiving normal feed), model group (receiving high-sugar and high-fat feed), and rimonabant group (receiving high-sugar and high-fat feed and rimonabant). At the end of the 4th or 8th week of experiment, 8 of each group were sacrificed. The body weight was measured, and the liver index was calculated. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and total cholesterol (TC) were determined. The serum levels of leptin and tumor necrosis factor (TNF)α were determined by ELISA. The liver tissue was treated by HE staining, and the pathological changes were observed. Immunohistochemical staining was used to evaluate the CB1 receptor expression in liver tissues in different stages of NAFLD. One-way analysis of variance and t-test were used for within-group and between-group comparisons. Pearson′s linear-correlation analysis was used for evaluating the correlation between indices. Results The model group had significantly higher serum levels of ALT, AST, TC, TG, leptin, and TNF-α than the control group and rimonabant group (P＜0.05). The model group showed simple fatty degeneration of the liver after 4 weeks and diffuse fatty degeneration of the liver with inflammatory cell infiltration after 8 weeks, while the rimonabant group had less severe liver lesions at the same time. CB1 receptor expression was not detected in the control group, but was detected in the model group and rimonabant group, according to the immunohistochemical staining, and the model group had a significantly higher integral optical density than the rimonabant group (P＜0.05). Conclusion The expression of CB1 receptors is enhanced in patients with NAFLD, and it may act together with TNF-α and leptin to promote the progression of NAFLD.