【Objective】 To study the effect of macrophage mediator 1 (MED1) deficiency on atherosclerosis in female mice. 【Methods】 ApoE knockout (ApoE^-/-), LDLR knockout (LDLR^-/-), MED1^fl/fl, and macrophage MED1 knockout (MED1^△Mac) mice were recruited in the study. Two types of mouse model were constructed:ApoE and macrophage MED1 double knockout (MED1^△Mac/ApoE^-/-) mice and their littermate controls (MED1^fl/fl/ApoE^-/-). ② LDLR knockout (LDLR^-/-) mice receiving bone marrow from MED1^△Mac (MED1^△Mac→LDLR^-/-) or MED1^fl/fl (MED1^fl/fl→LDLR^-/-) mice. Female mice from these two models were fed a Western diet (21% fat and 0.15% cholesterol) for 12 weeks to promote the development of atherosclerosis. Body weight, total cholesterol (TC), and total triglyceride (TG) content in plasma were measured dynamically. After Western diet feeding for 12 weeks, aortic tree and aortic root were collected and hematoxylin-eosin (H&E) and oil red O staining were performed. 【Results】 Plasma TC and TG did not significantly differ between MED1^fl/fl/ApoE^-/- control group and MED1^△Mac/ApoE^-/-experimental group. However, the plaque area in aortic tree and aortic root was significantly increased in MED1^△Mac/ApoE^-/-mice. Moreover, compared with that in MED1^fl/fl→LDLR^-/- control group, the plaque area of aortic tree and aortic root had an increasing trend in MED1^△Mac→LDLR^-/- mice group. 【Conclusion】 MED1 deficiency in macrophages promotes the development of atherosclerosis in female ApoE or LDLR knockout mice.