Disorders of lipid metabolism and inflammation play an important role in atherosclerosis. LongShengZhi (LSZ) capsule, a Chinese herbal medicine, has been used for treatment of patients with vascular diseases for many years. In this article, we determined the effect of LSZ on the progression of established atherosclerotic lesions in apoE-deficient (apoE) mice. ApoE mice were prefed high-fat diet (HFD) for 8 weeks to induce atherosclerosis, then started with LSZ treatment contained in HFD for 10 weeks. Although LSZ had little effect on HFD-induced hypercholesterolemia, it substantially reduced en face and sinus aortic lesions. The reduction of lesions was associated with reduced macrophage/foam cell accumulation by activating ABCA1/ABCG1 expression. LSZ maintained the integrity of arterial wall by increasing collagen or smooth muscle cell content and inhibiting cell apoptosis. LSZ also attenuated HFD-induced fatty liver by down-regulating expression of lipogenic and cholesterol synthetic genes while activating expression of triglyceride catabolism genes. Moreover, LSZ demonstrated potent anti-inflammatory effects. In vivo, LSZ reduced serum TNF-α levels, infiltration of neutrophils, Kupffer cells, and expression of inflammatory cytokines in the liver. In vitro, it inhibited lipopolysaccharide or palmitate-induced expression of inflammatory cytokines in macrophages. Therefore, LSZ reduces atherosclerosis by ameliorating hepatic lipid metabolism and inhibiting inflammation.